T3D3778 - Paspalitrem B
| Record Information | |
|---|---|
| Version | 1.0 |
| Creation Date | 2010-06-10 15:41:04 UTC |
| Update Date | 2013-04-25 08:49:00 UTC |
| Accession Number | T3D3778 |
| Identification | |
| Common Name | Paspalitrem B |
| Description | Paspalitrem B is a tremorgenic mycotoxin that has been found in fungi of the genera Penicillium and Aspergillus. It may be found in contaminated cereal crops such as oats, barley, millet, corn and rice. Tremorgenic mycotoxins affect central nervous system activity and have been implicated in a number of neurologic diseases of cattle collectively known as "staggers syndromes". (W824) |
| Compound Type |
|
| Chemical Structure |
|
| Synonyms | Not Available |
| Chemical Formula | C32H39NO5 |
| Average Molecular Weight | 517.6558 |
| Monoisotopic Molecular Weight | 517.282823363 |
| Chemical IUPAC Name | 19-hydroxy-11-[(1E)-3-hydroxy-3-methylbut-1-en-1-yl]-4,5,24,24-tetramethyl-25,26-dioxa-7-azaheptacyclo[21.2.1.0^{1,20}.0^{4,19}.0^{5,16}.0^{6,14}.0^{8,13}]hexacosa-6(14),8,10,12,20-pentaen-22-one |
| CAS Registry Number | 63764-58-9 |
| SMILES | CC(C)(O)\C=C\C1=CC2=C(NC3=C2CC2CCC4(O)C5=CC(=O)C6OC5(CCC4(C)C32C)OC6(C)C)C=C1 |
| InChI Identifier | InChI=1S/C32H39NO5/c1-27(2,35)11-9-18-7-8-22-20(15-18)21-16-19-10-12-31(36)24-17-23(34)26-28(3,4)38-32(24,37-26)14-13-29(31,5)30(19,6)25(21)33-22/h7-9,11,15,17,19,26,33,35-36H,10,12-14,16H2,1-6H3/b11-9+ |
| InChI Key | InChIKey=BZJWARDOYGJZHQ-PKNBQFBNSA-N |
| Chemical Taxonomy | |
| Kingdom | Organic Compounds |
| Super Class | Heterocyclic Compounds |
| Class | Naphthopyrans |
| Sub Class | Not Available |
| Direct Parent | Naphthopyrans |
| Alternative Parents |
|
| Molecular Framework | Aromatic Heteropolycyclic Compounds |
| Substituents |
|
| External Descriptors | Not Available |
| External Links | |
| DrugBank ID | Not Available |
| PubChem Compound ID | Not Available |
| KEGG ID | Not Available |
| UniProt ID | Not Available |
| OMIM ID | Not Available |
| ChEBI ID | Not Available |
| BioCyc ID | Not Available |
| CTD ID | Not Available |
| Stitch ID | Not Available |
| PDB ID | Not Available |
| ACToR ID | Not Available |
| Wikipedia Link | Not Available |
| Physical Properties | |
| Appearance | Not Available |
| Melting Point | Not Available |
| Solubility | Not Available |
| Predicted LogP | 4.9061189243333345 |
| Toxicity Profile | |
| Route of Exposure | Oral, dermal, inhalation, and parenteral (contaminated drugs). (W967) |
| Mechanism of Action | Tremorgenic mycotoxins exert their toxic effects by interfering with neurotransmitter release, possibly by causing degeneration of nerve terminals. They 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. In addition, paspalitrem B inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W824, W845) |
| Metabolism | Not Available |
| Toxicity Values | Not Available |
| Lethal Dose | Not Available |
| Carcinogenicity (IARC Classification) | Not Available |
| Uses/Sources | Paspalitrem B is a tremorgenic mycotoxin that has been found in fungi of the genera Penicillium and Aspergillus. It may be found in contaminated cereal crops such as oats, barley, millet, corn and rice. (W824) |
| Minimum Risk Level | Not Available |
| Health Effects | Tremorgenic mycotoxins affect central nervous system activity. They cause a neurological disease of cattle known as "staggers syndrome". (W824) |
| Symptoms | Tremorgenic mycotoxins affect central nervous system activity, inducing neurologic symptoms including mental confusion, paralysis, tremors, seizures, and death. They cause a neurological disease of cattle known as "staggers syndrome", which is characterized by muscle tremors, hyperexcitability, convulsions and ataxia. (W824) |
| Treatment | To control severe tremors caused by tremorgenic mycotoxins, methocarbamol should be administered. Generalized seizures may be treated with diazepam followed by methocarbamol or a barbiturate such as pentobarbital sodium. Gastric lavage should be performed and activated charcoal administered to limit further absorption of toxins. (W825) |
| References | |
| General References |
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Targets
1. 4-aminobutyrate aminotransferase, mitochondrial
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.
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. (W824)UniProt ID: P80404
Gene: ABAT
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
2. Gamma-aminobutyric acid receptor subunit alpha-1
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.
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. (W824)UniProt ID: P14867
Gene: GABRA1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
3. Gamma-aminobutyric acid receptor subunit alpha-2
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.
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. (W824)UniProt ID: P47869
Gene: GABRA2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
4. Gamma-aminobutyric acid receptor subunit alpha-3
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.
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. (W824)UniProt ID: P34903
Gene: GABRA3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
5. Gamma-aminobutyric acid receptor subunit alpha-4
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.
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. (W824)UniProt ID: P48169
Gene: GABRA4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
6. Gamma-aminobutyric acid receptor subunit alpha-5
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.
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. (W824)UniProt ID: P31644
Gene: GABRA5
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
7. Gamma-aminobutyric acid receptor subunit alpha-6
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.
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. (W824)UniProt ID: Q16445
Gene: GABRA6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
8. Gamma-aminobutyric acid receptor subunit beta-1
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.
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. (W824)UniProt ID: P18505
Gene: GABRB1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
9. Gamma-aminobutyric acid receptor subunit beta-2
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.
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. (W824)UniProt ID: P47870
Gene: GABRB2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
10. Gamma-aminobutyric acid receptor subunit beta-3
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.
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. (W824)UniProt ID: P28472
Gene: GABRB3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
11. Gamma-aminobutyric acid receptor subunit delta
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.
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. (W824)UniProt ID: O14764
Gene: GABRD
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
12. Gamma-aminobutyric acid receptor subunit epsilon
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.
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. (W824)UniProt ID: P78334
Gene: GABRE
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
13. Gamma-aminobutyric acid receptor subunit gamma-1
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.
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. (W824)UniProt ID: Q8N1C3
Gene: GABRG1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
14. Gamma-aminobutyric acid receptor subunit gamma-2
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.
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. (W824)UniProt ID: P18507
Gene: GABRG2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
15. Gamma-aminobutyric acid receptor subunit gamma-3
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.
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. (W824)UniProt ID: Q99928
Gene: GABRG3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
16. Gamma-aminobutyric acid receptor subunit pi
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.
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. (W824)UniProt ID: O00591
Gene: GABRP
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
17. Gamma-aminobutyric acid receptor subunit rho-1
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.
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. (W824)UniProt ID: P24046
Gene: GABRR1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
18. Gamma-aminobutyric acid receptor subunit rho-2
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.
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. (W824)UniProt ID: P28476
Gene: GABRR2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
19. Gamma-aminobutyric acid receptor subunit rho-3
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 (By similarity).
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. (W824)UniProt ID: A8MPY1
Gene: GABRR3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
20. Gamma-aminobutyric acid receptor subunit theta
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.
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. (W824)UniProt ID: Q9UN88
Gene: GABRQ
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
21. Gamma-aminobutyric acid type B receptor subunit 1
Receptor for GABA. The activity of this receptor is mediated by G-proteins that inhibit adenylyl cyclase activity, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipids hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA-B-R inhibit neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA-B-R decrease 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 function may be to regulate the availability of functional GABA-B-R1A/GABA-B-R2 heterodimers by competing for GABA-B-R2 dimerization. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.
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. (W824)UniProt ID: Q9UBS5
Gene: GABBR1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
22. Gamma-aminobutyric acid type B receptor subunit 2
Receptor for GABA. The activity of this receptor is mediated by G-proteins that inhibit adenylyl cyclase activity, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipids hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA-B-R inhibit neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA-B-R decrease 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.
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. (W824)UniProt ID: O75899
Gene: GABBR2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W824 — 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 ]
23. Calcium-activated potassium channel subunit alpha-1
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).
Paspalitrems inhibit presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W845)UniProt ID: Q12791
Gene: KCNMA1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W845 — 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 ]
24. Calcium-activated potassium channel subunit beta-1
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.
Paspalitrems inhibit presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W845)UniProt ID: Q16558
Gene: KCNMB1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W845 — 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 ]
25. Calcium-activated potassium channel subunit beta-2
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.
Paspalitrems inhibit presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W845)UniProt ID: Q9Y691
Gene: KCNMB2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W845 — 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 ]
26. Calcium-activated potassium channel subunit beta-3
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.
Paspalitrems inhibit presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W845)UniProt ID: Q9NPA1
Gene: KCNMB3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W845 — 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 ]
27. Calcium-activated potassium channel subunit beta-4
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.
Paspalitrems inhibit presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W845)UniProt ID: Q86W47
Gene: KCNMB4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W845 — 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 ]