Record Information
Version 1.0
Creation Date 2010-06-10 09:41:04 -0600
Update Date 2014-08-11 10:36:21 -0600
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". (A2976)
Compound Type
  • Organic Compound
  • Mycotoxin
Chemical Structure
Thumb
Synonyms Not Available
Chemical Formula C32H39NO5
Average Molecular Weight 517.6558
Monoisotopic Molecular Weight 517.282823363
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
Traditional 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
  • Naphthalenes
  • Indoles
  • Styrenes
  • Dihydropyranones
  • Cyclohexanols
  • Tertiary Alcohols
  • 1,3-Dioxolanes
  • Pyrroles
  • Ketones
  • Cyclic Alcohols and Derivatives
  • Cycloalkenes
  • Acetals
  • Organonitrogen Compounds
Molecular Framework Aromatic Heteropolycyclic Compounds
Substituents
  • benzene
  • naphthalene
  • cycloalkene
  • organonitrogen compound
  • ketone
  • acene
  • cyclohexanol
  • cyclic alcohol
  • acetal
  • alcohol
  • tertiary alcohol
  • styrene
  • pyrrole
  • indole
  • pyran
  • indole or derivative
  • meta-dioxolane
  • dihydropyranone
External Descriptors Not Available
Biological Properties
Status Unknown/Not Detected
Origin Not Available
Cellular Locations Not Available
Biofluid Locations Not Available
Tissue Locations Not Available
Pathways Not Available
Physical Properties
State Not Available
Appearance Not Available
Experimental Properties
Property Value
Melting Point Not Available
Boiling Point Not Available
Solubility Not Available
LogP Not Available
Predicted Properties
PropertyValueSource
water solubility3.47e-04 g/lALOGPS
logP4.62ALOGPS
logP4.91ChemAxon
logS-6.2ALOGPS
pKa (strongest acidic)13.6ChemAxon
pKa (strongest basic)-2.8ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count3ChemAxon
polar surface area91.78ChemAxon
rotatable bond count2ChemAxon
refractivity147.48ChemAxon
polarizability59.82ChemAxon
Spectra
Spectra Not Available
Toxicity Profile
Route of Exposure Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)
Mechanism of Toxicity 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. (A2976, A2993)
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. (A2976)
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". (A2976)
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. (A2976)
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. (T318)
Normal Concentrations
Not Available
DrugBank ID Not Available
HMDB ID Not Available
PubChem Compound ID Not Available
ChEMBL ID Not Available
ChemSpider 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
References
General References
  • A2976 — 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 ]
  • A2993 — 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 ]
  • A3101 — Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  • T318 — Schell MM. Tremorgenic mycotoxin intoxication. Veterinary Medicine. 2000.

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. (A2976)
UniProt ID: P80404
Gene: ABAT
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P14867
Gene: GABRA1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P47869
Gene: GABRA2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P34903
Gene: GABRA3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P48169
Gene: GABRA4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P31644
Gene: GABRA5
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: Q16445
Gene: GABRA6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P18505
Gene: GABRB1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P47870
Gene: GABRB2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P28472
Gene: GABRB3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: O14764
Gene: GABRD
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P78334
Gene: GABRE
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: Q8N1C3
Gene: GABRG1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P18507
Gene: GABRG2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: Q99928
Gene: GABRG3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: O00591
Gene: GABRP
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P24046
Gene: GABRR1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: P28476
Gene: GABRR2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: A8MPY1
Gene: GABRR3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: Q9UN88
Gene: GABRQ
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: Q9UBS5
Gene: GABBR1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2976)
UniProt ID: O75899
Gene: GABBR2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2976 — 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. (A2993)
UniProt ID: Q12791
Gene: KCNMA1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2993 — 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. (A2993)
UniProt ID: Q16558
Gene: KCNMB1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2993 — 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. (A2993)
UniProt ID: Q9Y691
Gene: KCNMB2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2993 — 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. (A2993)
UniProt ID: Q9NPA1
Gene: KCNMB3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2993 — 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. (A2993)
UniProt ID: Q86W47
Gene: KCNMB4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A2993 — 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 ]