BIPHASIC GABA-A RECEPTOR-MEDIATED EFFECT ON THE SPONTANEOUS ACTIVITY OF THE CIRCULAR LAYER IN CAT TERMINAL ILEUM

1. The GABA and GABA-A receptor agonist muscimol changed the spontaneo us mechanical activity of a circular layer isolated from cat terminal ileum, while the selective GABA-B receptor agonist (+/-)baclofen had n o effect. 2. GABA at doses ranging from 1 muM to 2 mM elicited concent ration-dependent biphasic responses which consisted of a relaxation fo llowed by contraction, with a tonic and a phasic comp values, calculat ed at 95% confidence limits (CL), were 94.9 muM (83.5-109.8 muM) and 6 6.0 muM (51.2-75.5 muM) for the relaxation and contractile phases, res pectively. 3. The GABA-induced biphasic responses were sensitive to bi cuculline and picrotoxinin and were entirely mimicked by muscimol. Bic uculline competitively antagonized the effects of GABA and gave closel y similar pA2 values for both phases of the responses-inhibitory and s timulatory. Cross-desensitization occurred only between GABA and musci mol and not between (+/-)baclofen and GABA, or (+/-)baclofen and musci mol. 4. Both bicuculline-sensitive phases evoked by GABA and muscimol were abolished by tetrodotoxin or atropine, but were unaffected by gua nethidine or naloxone. 5. The present results suggested that the bipha sic GABA effect on the mechanical activity of the circular layer in ca t terminal ileum was mediated by prejunctional GABA-A receptors, most probably through an action on the cholinergic pathway.