Role of peripheral GABAB receptors in the regulation of pepsinogen secretion in anaesthetized rats

The purpose of the present study was to investigate the role played by GABAB receptors in the regulation of gastric basal pepsinogen secretion in anaesthetized rats. Following parenteral administration, the GABAB receptor agonists (-)-baclofen and 3-aminopropylphosphinic acid (3-APPA) caused a dose-dependent increase in basal pepsinogen secretion which was associated with a parallel increment in acid output. The gastric stimulant effects induced by both agonists were not affected by intracerebroventricular injection of the GABAB 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 pepsinogen and acid output, were fully prevented by omeprazole or cimetidine, partly reduced by atropine and unaffected by pretreatment with capsaicin. When tested on rats undergoing bilateral cervical vagotomy, both (-)-baclofen and 3-APPA were still able to stimulate the basal pepsinogen and acid secretions, although at a lesser extent than in animals with intact vagus nerves. The stimulant actions elicited by (-)-baclofen in vagotomized rats were antagonized by 2-hydroxy-saclofen or CGP 35348, but not phaclofen. Moreover, these gastric excitatory effects were prevented by cimetidine or compound 48/80, while being unaffected by atropine. The present results show that peripheral GABAB receptors mediate an excitatory effect on gastric pepsinogen secretion which totally depends on an increase in acid output. It is also suggested that both vagal cholinergic and extravagal pathways, probably histaminergic in nature, take part in these GABAB receptor-mediated gastric stimulant actions.