In isolated segments of guinea-pig small intestine, γ-aminobutyric acid (GABA) (3-300 μM), the GABAA receptor agonist 3-aminopropane sulphonic acid (3-APS) (3-300 μM) and ivermectin (1-300 μM) caused concentration-dependent nerve-mediated cholinergic contractions sensitive to tetrodotoxin (1 μM) and hyoscine (1 μM). The EC50 values were 30.2±4.3, 24.6±3.1 and 4.8±0.6 μM, respectively. Picrotoxinin (10 μM), an allosteric blocker of the Cl- channel associated with GABAA receptors, non-competitively antagonized the contractile response caused by each agonist. Like picrotoxinin, lindane (10, 30 μM) caused a dose-related shift to the right of the concentration-response curve to GABA, 3-APS and ivermectin with depression of the maximum response. SR 95531 (3 μM), a competitive antagonist of GABAA receptors, caused a parallel dextral shift of the concentration-response curve to ivermectin with an apparent single point pA2 value of 6.5. Our results suggest that ivermectin and lindane, two neurotoxic pesticides interfering with central GABAergic transmission, exert agonist and non-competive antagonist properties at the enteric GABAA receptor-ionophore complex. This peripheral complex can thus be considered as an additional target for the action of both these compounds.
|Number of pages||6|
|Journal||European Journal of Pharmacology: Environmental Toxicology and|
|Publication status||Published - Jun 1 1993|
- Enteric GABA receptors
- GABA (γ-aminobutyric acid)
- Small intestine (guinea-pig)
ASJC Scopus subject areas