Penitrem C
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Basic Info
| Common Name | Penitrem C(F04981) |
| 2D Structure | |
| Description | Penitrem C is a tremorgenic mycotoxin and neurotoxin produced by certain species of Aspergillus, Claviceps, and Penicillium. Penicillium crustosum in particular is a common foodborne fungus that causes spoilage in a wide variety of foods, including meat, cereals, nuts, cheese, eggs, fruit, and processed and refrigerated foods. Tremorgenic mycotoxins affect central nervous system activity and have been implicated in a number of neurologic diseases of horses and cattle collectively known as "staggers syndromes". (L1959, A2989) |
| FRCD ID | F04981 |
| CAS Number | 37318-84-6 |
| PubChem CID | 119470 |
| Formula | C37H44ClNO4 |
| IUPAC Name | None |
| InChI Key | BVVRIERIEDMORG-UHFFFAOYSA-N |
| InChI | InChI=1S/C37H44ClNO4/c1-16(2)31-25(40)14-21-26(42-31)9-10-35(6)36(7)20(8-11-37(21,35)41)32-30-29-24(39-33(30)36)15-23(38)19-12-17(3)18-13-22(27(18)28(19)29)34(4,5)43-32/h14-15,18,20,22,25-27,31-32,39-41H,1,3,8-13H2,2,4-7H3 |
| Canonical SMILES | CC(=C)C1C(C=C2C(O1)CCC3(C2(CCC4C3(C5=C6C4OC(C7CC8C7C9=C6C(=CC(=C9CC8=C)Cl)N5)(C)C)C)O)C)O |
| Isomeric SMILES | CC(=C)C1C(C=C2C(O1)CCC3(C2(CCC4C3(C5=C6C4OC(C7CC8C7C9=C6C(=CC(=C9CC8=C)Cl)N5)(C)C)C)O)C)O |
| Synonyms |
12-chloro-14b,14c,17,17-tetramethyl-10-methylidene-2-(prop-1-en-2-yl)-2,3,5,6,6a,7,7d,8,9,9a,10,11,14,14b,14c,15,16,16a-octadecahydro-4bh-7,8-(epoxymethano)chromeno[5',6':6,7]indeno[1,2-b]cyclobuta[5,6]benzo[1,2-e]indole-3,4b-diol
Penitrem C
UNII-5GTV3VH5D6
5GTV3VH5D6
37318-84-6
AC1L3OVQ
AC1Q3T4S
7,8-(Epoxymethano)-4bH-1-benzopyrano(5',6':6,7)indeno(1,2-b)cyclobuta(5,6)benz(1,2-e)indole-3,4b-diol, 12-chloro-2,3,5,6,6a,7,7d,8,9,9a,10,11,14,14b,14c,15,16,16a-octadecahydro-14b,14c,17,17-tetramethyl-10-methylene-2-(1-methylethenyl)-, (2R,3R,4bR,6aR,7S,7dS,8S,9aS,14bS,14cR,16aS)-
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Naphthopyrans |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Naphthopyrans |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Naphthopyran - Naphthalene - Tetralin - 3-alkylindole - Indole - Indole or derivatives - Aryl chloride - Aryl halide - Pyran - Benzenoid - Tertiary alcohol - Pyrrole - Heteroaromatic compound - Cyclic alcohol - Secondary alcohol - Azacycle - Oxacycle - Dialkyl ether - Ether - Alcohol - Organopnictogen compound - Organic oxygen compound - Organic nitrogen compound - Hydrocarbon derivative - Organohalogen compound - Organochloride - Organonitrogen compound - Organooxygen compound - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as naphthopyrans. These are compounds containing a pyran ring fused to a naphthalene moiety. Furan is a 6 membered-ring non-aromatic ring with five carbon and one oxygen atoms. Naphthalene is a polycyclic aromatic hydrocarbon made up of two fused benzene rings. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 602.212 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 1 |
| Complexity | 1330 |
| Monoisotopic Mass | 601.296 |
| Exact Mass | 601.296 |
| XLogP | 5 |
| Formal Charge | 0 |
| Heavy Atom Count | 43 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 11 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.8265 |
| Human Intestinal Absorption | HIA+ | 0.9942 |
| Caco-2 Permeability | Caco2+ | 0.5052 |
| P-glycoprotein Substrate | Substrate | 0.8047 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.6974 |
| Non-inhibitor | 0.9118 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8180 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.5200 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8942 |
| CYP450 2D6 Substrate | Non-substrate | 0.8090 |
| CYP450 3A4 Substrate | Substrate | 0.7153 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.6455 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.7805 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8770 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7126 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8841 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.5311 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9399 |
| Non-inhibitor | 0.8646 | |
| AMES Toxicity | Non AMES toxic | 0.6425 |
| Carcinogens | Non-carcinogens | 0.9319 |
| Fish Toxicity | High FHMT | 0.9995 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9960 |
| Honey Bee Toxicity | High HBT | 0.5571 |
| Biodegradation | Not ready biodegradable | 1.0000 |
| Acute Oral Toxicity | III | 0.5455 |
| Carcinogenicity (Three-class) | Non-required | 0.4361 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -4.5803 | LogS |
| Caco-2 Permeability | 1.0235 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.5762 | LD50, mol/kg |
| Fish Toxicity | 0.6254 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.8882 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Detection of the Cytotoxic Penitrems A-F in Cheese from the European Single Market by HPLC-MS/MS. | J Agric Food Chem | 2018 Feb 7 | 29338236 |
| Several species of Penicillium isolated from chestnut flour processing are pathogenic on fresh chestnuts and produce mycotoxins. | Food Microbiol | 2018 Dec | 30166166 |
| Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A. | Mar Drugs | 2016 Nov 9 | 27834847 |
| Production of the Fusarium Mycotoxin Moniliformin by Penicillium melanoconidium. | J Agric Food Chem | 2016 Jun 8 | 27195914 |
| Modeling Growth and Toxin Production of Toxigenic Fungi Signaled in Cheese under Different Temperature and Water Activity Regimes. | Toxins (Basel) | 2016 Dec 24 | 28029129 |
| Neurotoxicity of Penicillium crustosum secondary metabolites: tremorgenic activity of orally administered penitrem A and thomitrem A and E in mice. | Toxicon | 2012 Dec 15 | 23085423 |
| Microscopic fungi recovered from honey and their toxinogenity. | J Environ Sci Health A Tox Hazard Subst Environ Eng | 2012 | 22702826 |
| Poisoning of dogs with tremorgenic Penicillium toxins. | Med Mycol | 2010 Feb | 19886763 |
| Using roquefortine C as a biomarker for penitrem A intoxication. | J Vet Diagn Invest | 2009 Mar | 19286504 |
| LC-MS/MS screen for penitrem A and roquefortine C in serum and urine samples. | Anal Chem | 2006 Jul 1 | 16808474 |
| The effect of substrate on mycotoxin production of selected Penicillium strains. | Int J Food Microbiol | 2005 Mar 15 | 15734568 |
| Isolation and metabolite production by Penicillium roqueforti, P. paneum and P. crustosum isolated in Canada. | Mycopathologia | 2005 Jun | 15983744 |
| The presence of Penicillium and Penicillium mycotoxins in food wastes. | Int J Food Microbiol | 2004 Jan 15 | 14698099 |
| Penicillium expansum: consistent production of patulin, chaetoglobosins, and other secondary metabolites in culture and their natural occurrence in fruit products. | J Agric Food Chem | 2004 Apr 21 | 15080656 |
| Penitrem and thomitrem formation by Penicillium crustosum. | Mycopathologia | 2004 Apr | 15180164 |
| Spoilage fungi and their mycotoxins in commercially marketed chestnuts. | Int J Food Microbiol | 2003 Nov 15 | 14527787 |
| Insecticidal activity of penitrems, including penitrem G, a new member of the family isolated from Penicillium crustosum. | J Agric Food Chem | 2003 Apr 9 | 12670149 |
| Cell cytotoxicity and mycotoxin and secondary metabolite production by common penicillia on cheese agar. | J Agric Food Chem | 2002 Oct 9 | 12358494 |
| Determination of Penicillium mycotoxins in foods and feeds using liquid chromatography-mass spectrometry. | J Chromatogr A | 2002 Jul 26 | 12198847 |
| Mycoflora and mycotoxins in Brazilian black pepper, white pepper and Brazil nuts. | Mycopathologia | 2000 Jan | 11229375 |
Targets
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations.
- Gene Name:
- KCNMB4
- Uniprot ID:
- Q86W47
- Molecular Weight:
- 23948.465 Da
- Mechanism of Action:
- Penitrems inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle.
References
- Knaus HG, McManus OB, Lee SH, Schmalhofer WA, Garcia-Calvo M, Helms LM, Sanchez M, Giangiacomo K, Reuben JP, Smith AB 3rd, et al.: Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. Biochemistry. 1994 May 17;33(19):5819-28. [7514038 ]
- General Function:
- Succinate-semialdehyde dehydrogenase binding
- Specific Function:
- Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine.
- Gene Name:
- ABAT
- Uniprot ID:
- P80404
- Molecular Weight:
- 56438.405 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Increases the apparent Ca(2+)/voltage sensitivity of the KCNMA1 channel. It also modifies KCNMA1 channel kinetics and alters its pharmacological properties. It slows down the activation and the deactivation kinetics of the channel. Acts as a negative regulator of smooth muscle contraction by enhancing the calcium sensitivity to KCNMA1. Its presence is also a requirement for internal binding of the KCNMA1 channel opener dehydrosoyasaponin I (DHS-1) triterpene glycoside and for external binding of the agonist hormone 17-beta-estradiol (E2). Increases the binding activity of charybdotoxin (CTX) toxin to KCNMA1 peptide blocker by increasing the CTX association rate and decreasing the dissociation rate.
- Gene Name:
- KCNMB1
- Uniprot ID:
- Q16558
- Molecular Weight:
- 21797.27 Da
- Mechanism of Action:
- Penitrems inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle.
References
- Knaus HG, McManus OB, Lee SH, Schmalhofer WA, Garcia-Calvo M, Helms LM, Sanchez M, Giangiacomo K, Reuben JP, Smith AB 3rd, et al.: Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. Biochemistry. 1994 May 17;33(19):5819-28. [7514038 ]
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Acts as a negative regulator that confers rapid and complete inactivation of KCNMA1 channel complex. May participate in KCNMA1 inactivation in chromaffin cells of the adrenal gland or in hippocampal CA1 neurons.
- Gene Name:
- KCNMB2
- Uniprot ID:
- Q9Y691
- Molecular Weight:
- 27129.37 Da
- Mechanism of Action:
- Penitrems inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle.
References
- Knaus HG, McManus OB, Lee SH, Schmalhofer WA, Garcia-Calvo M, Helms LM, Sanchez M, Giangiacomo K, Reuben JP, Smith AB 3rd, et al.: Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. Biochemistry. 1994 May 17;33(19):5819-28. [7514038 ]
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Alters the functional properties of the current expressed by the KCNMA1 channel. Isoform 2, isoform 3 and isoform 4 partially inactivate the current of KCNBMA. Isoform 4 induces a fast and incomplete inactivation of KCNMA1 channel that is detectable only at large depolarizations. In contrast, isoform 1 does not induce detectable inactivation of KCNMA1. Two or more subunits of KCNMB3 are required to block the KCNMA1 tetramer.
- Gene Name:
- KCNMB3
- Uniprot ID:
- Q9NPA1
- Molecular Weight:
- 31603.26 Da
- Mechanism of Action:
- Penitrems inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle.
References
- Knaus HG, McManus OB, Lee SH, Schmalhofer WA, Garcia-Calvo M, Helms LM, Sanchez M, Giangiacomo K, Reuben JP, Smith AB 3rd, et al.: Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. Biochemistry. 1994 May 17;33(19):5819-28. [7514038 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
- Gene Name:
- GABRA1
- Uniprot ID:
- P14867
- Molecular Weight:
- 51801.395 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRA3
- Uniprot ID:
- P34903
- Molecular Weight:
- 55164.055 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRA4
- Uniprot ID:
- P48169
- Molecular Weight:
- 61622.645 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Transporter activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRA5
- Uniprot ID:
- P31644
- Molecular Weight:
- 52145.645 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRA6
- Uniprot ID:
- Q16445
- Molecular Weight:
- 51023.69 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Ligand-gated ion channel activity
- Specific Function:
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
- Gene Name:
- GABRB1
- Uniprot ID:
- P18505
- Molecular Weight:
- 54234.085 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
- Gene Name:
- GABRB2
- Uniprot ID:
- P47870
- Molecular Weight:
- 59149.895 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Gaba-gated chloride ion channel activity
- Specific Function:
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
- Gene Name:
- GABRB3
- Uniprot ID:
- P28472
- Molecular Weight:
- 54115.04 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRE
- Uniprot ID:
- P78334
- Molecular Weight:
- 57971.175 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRG1
- Uniprot ID:
- Q8N1C3
- Molecular Weight:
- 53594.49 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
- Gene Name:
- GABRG2
- Uniprot ID:
- P18507
- Molecular Weight:
- 54161.78 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRG3
- Uniprot ID:
- Q99928
- Molecular Weight:
- 54288.16 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Gaba-a receptor activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. In the uterus, the function of the receptor appears to be related to tissue contractility. The binding of this pI subunit with other GABA(A) receptor subunits alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone.
- Gene Name:
- GABRP
- Uniprot ID:
- O00591
- Molecular Weight:
- 50639.735 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Gaba-a receptor activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-1 GABA receptor could play a role in retinal neurotransmission.
- Gene Name:
- GABRR1
- Uniprot ID:
- P24046
- Molecular Weight:
- 55882.91 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Gaba-a receptor activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-2 GABA receptor could play a role in retinal neurotransmission.
- Gene Name:
- GABRR2
- Uniprot ID:
- P28476
- Molecular Weight:
- 54150.41 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Transmembrane signaling receptor activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRQ
- Uniprot ID:
- Q9UN88
- Molecular Weight:
- 72020.875 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- G-protein coupled gaba receptor activity
- Specific Function:
- Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception.
- Gene Name:
- GABBR2
- Uniprot ID:
- O75899
- Molecular Weight:
- 105820.52 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).
- Gene Name:
- KCNMA1
- Uniprot ID:
- Q12791
- Molecular Weight:
- 137558.115 Da
- Mechanism of Action:
- Penitrems inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle.
References
- Knaus HG, McManus OB, Lee SH, Schmalhofer WA, Garcia-Calvo M, Helms LM, Sanchez M, Giangiacomo K, Reuben JP, Smith AB 3rd, et al.: Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. Biochemistry. 1994 May 17;33(19):5819-28. [7514038 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRA2
- Uniprot ID:
- P47869
- Molecular Weight:
- 51325.85 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Gaba-a receptor activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRD
- Uniprot ID:
- O14764
- Molecular Weight:
- 50707.835 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- Gaba-a receptor activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRR3
- Uniprot ID:
- A8MPY1
- Molecular Weight:
- 54271.1 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
- General Function:
- G-protein coupled gaba receptor activity
- Specific Function:
- Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen.Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.
- Gene Name:
- GABBR1
- Uniprot ID:
- Q9UBS5
- Molecular Weight:
- 108319.4 Da
- Mechanism of Action:
- Tremorgenic mycotoxins are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse.
References
- Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]