ROLE OF PERIPHERAL GABA(B) RECEPTORS IN THE REGULATION OF PEPSINOGEN SECRETION IN ANESTHETIZED RATS

The purpose of the present study was to investigate the role played by GABA(B) receptors in the regulation of gastric basal pepsinogen secre tion in anaesthetized rats. Following parenteral administration, the G ABA(B) receptor agonists(-)-baclofen and 3-aminopropylphosphinic acid (3-APPA) caused a dose-dependent increase in basal pepsinogen secretio n which was associated with a parallel increment in acid output. The g astric stimulant effects induced by both agonists were not affected by intracerebroventricular injection of the GABA(B) receptor antagonists 2-hydroxy-saclofen, 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP 35348) or phaclofen, whereas the excitatory actions were antagonized by intravenously administered 2-hydroxy-saclofen or CGP 35348, but not phaclofen. In addition, the (-)-baclofen-induced increases in both pe psinogen and acid output, were fully prevented by omeprazole or cimeti dine, partly reduced by atropine and unaffected by pretreatment with c apsaicin. When tested on rats undergoing bilateral cervical vagotomy, both (-)-baclofen and 3-APPA were still able to stimulate the basal pe psinogen and acid secretions, although at a lesser extent than in anim als with intact vagus nerves. The stimulant actions elicited by(-)-bac lofen in vagotomized rats were antagonized by 2-hydroxy-saclofen or CG P 35348, but not phaclofen. Moreover, these gastric excitatory effects were prevented by cimetidine or compound 48/50, while being unaffecte d by atropine. The present results show that peripheral GABA(B) recept ors mediate an excitatory effect on gastric pepsinogen secretion which totally depends on an increase in acid output. It is also suggested t hat both vagal cholinergic and extravagal pathways, probably histamine rgic in nature, take part in these GABA(B) receptor-mediated gastric s timulant actions.