The stimulatory effect of forskolin on gastric acid secretion in rats

Adenylate cyclase is involved in the histamine pathway of the parietal cell. We therefore studied the effect of forskolin, a direct activator of the membrane-bound adenylate cyclase, on gastric acid secretion in anaesthetized rats. Forskolin in the range of 0.1-1 mg/kg i.v. caused a dose-dependent stimulation of acid secretion. Higher doses were not tolerated. The duration of action of the forskolin-induced acid secretion was also dose-related. The combined infusion of forskolin (0.3 mg/kg per h i.v.) and histamine at a low rate (0.5 mg/kg per h i.v.) produced a maximal stimulation of acid secretion which was comparable to that with a histamine infusion of 10 mg/kg per h i.v. without forskolin. Administration of desglugastrin at a low rate (10 micrograms/kg per h i.v.) plus forskolin by i.v. infusion produced similar results. In contrast, infusion of carbachol (3 micrograms/kg per h i.v.) together with forskolin caused only an additive effect on acid secretion. Including an isobutyl-methyl-xanthine (IBMX) i.v. injection of 3 mg/kg at the beginning of the forskolin infusion (0.3 mg/kg per h i.v.) produced an acid output after 60 min which was approximately 50% of the maximal stimulation during a histamine (10 mg/kg per h i.v.) infusion. The IBMX/forskolin-induced stimulation was completely inhibited by 0.5 mg/kg omeprazole i.v. while the equipotent antisecretory dose (during histamine stimulation) of cimetidine caused only a weak decrease in acid output.