Phaclofen-sensitive GABA-B receptors do not mediate excitatory effects of baclofen on gastric secretion

Abstract

The present study investigates the effects of centrally or peripherally administered baclofen on gastric acid secretion from pylorus-ligated rats. The influence of baclofen on basal acid secretion from isolated guinea-pig gastric fundus was also evaluated. At all doses employed, intracerebroventricular baclofen significantly decreased acid secretion, this inhibitory action being antagonized by intracerebroventricular phaclofen. Intravenous baclofen induced both gastric inhibitory and excitatory responses at low and high doses, respectively. Intracerebroventricular phaclofen prevented the inhibitory effect, while neither intracerebroventricular nor intravenous phaclofen modified the stimulant action of parenteral baclofen. Both central and parenteral muscimol did not influence gastric acid secretion. Moreover, baclofen or muscimol were without effect on basal acid secretion from isolated guinea-pig gastric fundus, whereas bethanechol caused a marked and concentration-dependent stimulant action. The present results provide further evidence for the inhibitory role of central phaclofen-sensitive GABA-B receptors in the regulation of acid secretion. In addition they indicate that the hypersecretory effect exerted by parenteral baclofen may depend upon the activation of putative peripheral non-A and phaclofen-insensitive GABA-B receptors. Finally, peripheral GABA receptors do not appear to be significantly involved in the direct control of gastric secretion.