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T3D3780 - Paxilline

Record Information
Version 1.0
Creation Date 2010-06-10 15:41:05 UTC
Update Date 2013-04-25 08:49:00 UTC
Accession Number T3D3780
Identification
Common Name Paxilline
Description Paxilline is a tremorgenic mycotoxin that has been found in fungus Penicillium paxilli. 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, W947)
Compound Type
  • Organic Compound
  • Mycotoxin
Chemical Structure
Thumb
MOL SDF SMILES InChI
Synonyms
  1. 2H-1-Benzopyrano(5',6':6,7)indeno(1,2-b)indol-3(4bh)-one, 5,6,6a,7,12,12b,12c,13,14,14a-decahydro-4b-hydroxy-2-(1-hydroxy-1-methylethyl)-12b,12c-dimethyl-, (2-alpha,4b-beta,6a-alpha,12b-beta,12c-alpha,14a-beta)-
  2. 2H-Pyrano(2'',3'':5',6')benz(1',2':6,7)indeno(1,2-b)indol-3(4bH)-one, 5,6,6a,7,12,12b,12c,13,14,14a-decahydro-4b-hydroxy-2-(1-hydroxy-1-methylethyl)-12b,12c-dimethyl-, (2R,4bS,6aS,12bS,12cR,14aS)-
Chemical Formula C27H33NO4
Average Molecular Weight 435.5552
Monoisotopic Molecular Weight 435.240958549
Chemical IUPAC Name
11-hydroxy-7-(2-hydroxypropan-2-yl)-1,2-dimethyl-6-oxa-23-azahexacyclo[12.10.0.0^{2,11}.0^{5,10}.0^{16,24}.0^{17,22}]tetracosa-9,16(24),17,19,21-pentaen-8-one
CAS Registry Number 57186-25-1
SMILES
CC(C)(O)C1OC2CCC3(C)C4(C)C(CC5=C4NC4=CC=CC=C54)CCC3(O)C2=CC1=O
InChI Identifier
InChI=1S/C27H33NO4/c1-24(2,30)23-20(29)14-18-21(32-23)10-11-25(3)26(4)15(9-12-27(18,25)31)13-17-16-7-5-6-8-19(16)28-22(17)26/h5-8,14-15,21,23,28,30-31H,9-13H2,1-4H3
InChI Key InChIKey=ACNHBCIZLNNLRS-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Heterocyclic Compounds
Class Naphthopyrans
Sub Class Not Available
Direct Parent Naphthopyrans
Alternative Parents
  • Naphthalenes
  • Indoles
  • Dihydropyranones
  • Cyclohexanols
  • Benzene and Substituted Derivatives
  • Tertiary Alcohols
  • Pyrroles
  • Ketones
  • Cyclic Alcohols and Derivatives
  • Cycloalkenes
  • Dialkyl Ethers
  • Organonitrogen Compounds
Molecular Framework Aromatic Heteropolycyclic Compounds
Substituents
  • benzene
  • naphthalene
  • cycloalkene
  • organonitrogen compound
  • dialkyl ether
  • ketone
  • acene
  • cyclohexanol
  • cyclic alcohol
  • alcohol
  • tertiary alcohol
  • pyrrole
  • indole
  • pyran
  • indole or derivative
  • dihydropyranone
External Descriptors Not Available
DrugBank ID Not Available
PubChem Compound ID 105008 Link_out
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 http://en.wikipedia.org/wiki/Paxilline Link_out
Physical Properties
Appearance Not Available
Melting Point Not Available
Solubility Not Available
Predicted LogP 3.6230832606666667
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, paxilline inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. Paxilline is also genotoxic and causes DNA damage. (W824, W845, W884)
Metabolism Not Available
Toxicity Values Not Available
Lethal Dose Not Available
Carcinogenicity (IARC Classification) Not Available
Uses/Sources Paxilline is a tremorgenic mycotoxin that has been found in fungus Penicillium paxilli. It may be found in contaminated cereal crops such as oats, barley, millet, corn and rice. (W824, W947)
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
  • 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 Link_out]
  • W825 — Schell MM. Tremorgenic mycotoxin intoxication. Veterinary Medicine. 2000.
  • 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 Link_out]
  • W884 — Sabater-Vilar M, Nijmeijer S, Fink-Gremmels J. Genotoxicity assessment of five tremorgenic mycotoxins (fumitremorgen B, paxilline, penitrem A, verruculogen, and verrucosidin) produced by molds isolated from fermented meats. J Food Prot. 2003 Nov;66(11):2123-9. [14627292 Link_out]
  • W966 — Wikipedia. Paxilline. Last Updated 23 March 2010. [Link]
  • W967 — Peraica M, Domijan AM. Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 Link_out]

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 Link_out
Gene: ABAT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRA3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRA5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRA6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRB3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRD Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRG1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRG3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRP Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRR2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRR3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABRQ Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABBR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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 Link_out
Gene: GABBR2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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).

Paxilline inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W845)
UniProt ID: Q12791 Link_out
Gene: KCNMA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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.

Paxilline inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W845)
UniProt ID: Q16558 Link_out
Gene: KCNMB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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.

Paxilline inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W845)
UniProt ID: Q9Y691 Link_out
Gene: KCNMB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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.

Paxilline inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W845)
UniProt ID: Q9NPA1 Link_out
Gene: KCNMB3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]

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.

Paxilline inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. (W845)
UniProt ID: Q86W47 Link_out
Gene: KCNMB4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
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 Link_out]