1165779

GABA receptors on the somatic muscle cells of the parasitic nematode, Ascaris suum: stereoselectivity indicates similarity to a GABAA-type agonist recognition site.

Article date: 1989/11/1

PubMed ID: 1165779

Journal name: British journal of pharmacology (ISSN: 0007-1188)

ABSTRACT

1. The gamma-aminobutyric acid (GABA) receptors on the somatic muscle cells of Ascaris, which mediate muscle cell hyperpolarization and relaxation, have been characterized by use of intracellular recording techniques. 2. These receptors are like mammalian GABAA-receptors in that the response is mediated by an increase conductance to chloride ions. The GABAA-mimetic, muscimol, has a relative potency of 0.40 +/- 0.02 (n = 3) compared to GABA. 3. The stereoselectivity of the GABA receptor on Ascaris is identical to that for the mammalian GABAA-receptor, as determined from the relative potency of three pairs of enantiomers of structural analogues of GABA. 4. The most potent agonist is (S)-(+)-dihydromuscimol which is 7.53 +/- 0.98 (n = 5) times more potent than GABA. 5. The Ascaris GABA receptor is not significantly blocked, at concentrations below 100 microM by the potent, competitive GABAA-receptor antagonist, SR95531. 6. The Ascaris GABA receptor does not recognise agents that are known to block the GABA gated chloride channel in mammalian preparations such as t-butylbicyclophosphorothionate (TBPS, 10 microM, n = 2) or the insecticide dieldrin (100 microM, n = 3). 7. GABAergic responses in Ascaris are not potentiated by pentobarbitone (100 microM, n = 3) or flurazepam (100 microM, n = 3). 8. The potencies of various GABA-mimetics in the Ascaris preparation have been compared with their potency at displacing GABAA-receptor binding in mammalian brain. Excluding the sulphonic acid derivatives of GABA, the correlation coefficient ® between the potencies of compounds in the two systems is 0.74 (P less than 0.01). The significance of this correlation is discussed. 9. The pharmacology of the Ascaris GABA receptor is discussed in relation to other invertebrate systems and the mammalian subclassification of GABA receptors.

Author List: Holden-Dye L, Krogsgaard-Larsen P, Nielsen L, Walker R J

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Receptors, GABA-A; gamma-Aminobutyric Acid; Baclofen; Dieldrin; Pentobarbital; Flurazepam;

Mesh terms: Animals; Ascaris/metabolism; Baclofen/pharmacology; Binding, Competitive/drug effects; Dieldrin/pharmacology; Electric Stimulation; Flurazepam/pharmacology; In Vitro Techniques; Membrane Potentials/drug effects; Muscles/cytology; Pentobarbital/pharmacology; Receptors, GABA-A/drug effects; Stereoisomerism; gamma-Aminobutyric Acid/analogs & derivatives;

Citations: - 4151806

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