Ligand structural specificity of GABAA receptors in guinea pig ileum

The ligand structural specificity of ileal GABAA receptors was examined using the strength and half-life of contractions in guinea-pig myenteric plexus-longitudinal muscle preparations. The agonists used differ by more than a factor of 1000 in affinity to central GABAA receptors and include both conformationally flexible and restricted molecules as well as pairs of enantiomers. The overall correlation between ileal contractile activity and rat brain receptor affinity was poor (r = 0.75), but within groups of conformationally flexible or conformationally restricted molecules a high correlation was found (r greater than 0.9999). When comparing data for ileal contractile activity with available data for agonist activity in the CNS no difference between ligand specificity of ileal and central GABAA receptors was apparent with the present range of ligands. The half-lives of ileal contractile responses were found to decrease with increasing GABAB agonist activity.