Janthitrem E
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Basic Info
| Common Name | Janthitrem E(F05007) |
| 2D Structure | |
| Description | Janthitrem E is produced by Penicillium janthinellum. Tremorgenic mycotoxin Janthitrem e belongs to the family of Diterpenes. These are terpene compounds formed by four isoprene units. |
| FRCD ID | F05007 |
| CAS Number | 90986-50-8 |
| PubChem CID | 10348646 |
| Formula | C37H49NO6 |
| IUPAC Name | None |
| InChI Key | TVRIMSLYKUNOPS-UHFFFAOYSA-N |
| InChI | InChI=1S/C37H49NO6/c1-32(2)17-23-19-15-25-20(14-21(19)29(40)28(23)34(5,6)44-32)22-13-18-9-12-37(42)24-16-26(39)31(33(3,4)41)43-27(24)10-11-35(37,7)36(18,8)30(22)38-25/h14-18,26-29,31,38-42H,9-13H2,1-8H3 |
| Canonical SMILES | CC1(C=C2C(C(C3=C2C=C4C(=C3)C5=C(N4)C6(C(C5)CCC7(C6(CCC8C7=CC(C(O8)C(C)(C)O)O)C)O)C)O)C(O1)(C)C)C |
| Isomeric SMILES | CC1(C=C2C(C(C3=C2C=C4C(=C3)C5=C(N4)C6(C(C5)CCC7(C6(CCC8C7=CC(C(O8)C(C)(C)O)O)C)O)C)O)C(O1)(C)C)C |
| Synonyms |
Janthitrem E
90986-50-8
|
| 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 - 3-alkylindole - Indane - Indole - Indole or derivatives - Pyran - Benzenoid - Cyclic alcohol - Tertiary alcohol - Pyrrole - Heteroaromatic compound - Secondary alcohol - Azacycle - Oxacycle - Dialkyl ether - Ether - Polyol - Organopnictogen compound - Organic oxygen compound - Organic nitrogen compound - Hydrocarbon derivative - Alcohol - 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 | 603.8 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 1 |
| Complexity | 1300 |
| Monoisotopic Mass | 603.356 |
| Exact Mass | 603.356 |
| XLogP | 3.1 |
| Formal Charge | 0 |
| Heavy Atom Count | 44 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 9 |
| 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+ | 0.8759 |
| Human Intestinal Absorption | HIA+ | 0.9945 |
| Caco-2 Permeability | Caco2- | 0.5235 |
| P-glycoprotein Substrate | Substrate | 0.8288 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.7421 |
| Non-inhibitor | 0.9041 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8420 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.4169 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8552 |
| CYP450 2D6 Substrate | Non-substrate | 0.7967 |
| CYP450 3A4 Substrate | Substrate | 0.7233 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.7972 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8898 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9130 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8833 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8888 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.5803 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9620 |
| Non-inhibitor | 0.8724 | |
| AMES Toxicity | Non AMES toxic | 0.6853 |
| Carcinogens | Non-carcinogens | 0.9679 |
| Fish Toxicity | High FHMT | 0.9711 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9941 |
| Honey Bee Toxicity | High HBT | 0.6679 |
| Biodegradation | Not ready biodegradable | 0.9882 |
| Acute Oral Toxicity | III | 0.5662 |
| Carcinogenicity (Three-class) | Non-required | 0.5075 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -4.3943 | LogS |
| Caco-2 Permeability | 0.8619 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.8626 | LD50, mol/kg |
| Fish Toxicity | 0.7235 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.8935 | pIGC50, ug/L |
Targets
- 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:
- 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:
- 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:
- 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:
- 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:
- 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:
- 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. 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:
- 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:
- 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:
- 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. 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 ]