THE MECHANISM OF INHIBITORY-ACTION OF SECRETIN ON GASTRIC-ACID SECRETION IN CONSCIOUS RATS

1. Secretin has been recognized as an important enterogastrone. In ord er to investigate the mechanism of secretin-induced inhibition of gast ric acid secretion, the effects of both antisomatostatin antibody and indomethacin on acid secretion were examined in conscious rats with ga stric cannulas. 2. Secretin given intravenously at 5.6 pmol kg(-1) h(- 1) inhibited profoundly the acid secretion stimulated by pentagastrin at 0.3 mu g kg(-1) h(-1). 3. When a rabbit antisomatostatin serum was given intravenously, it not only abolished the secretin-induced inhibi tion on the pentagastrin-stimulated acid secretion, but also augmented both basal and pentagastrin-stimulated acid secretion. 4. Indomethaci n also significantly augmented basal acid secretion, starting 45 min a fter the drug delivery began. It reversed the secretin-induced inhibit ion but it did not augment the pentagastrin-stimulated acid secretion. 5. Neither antisomatostatin serum influenced prostaglandin E(2)-induc ed inhibition of the pentagastrin-stimulated acid secretion, nor did i ndomethacin affect the inhibition by somatostatin, suggesting strongly that the inhibition by somatostatin is not mediated by endogenous pro staglandins, nor is that by prostaglandins E(2) mediated by endogenous somatostatin. 6. It is concluded that the inhibitory action of secret in on pentagastrin-stimulated gastric acid secretion is mediated by bo th somatostatin and prostaglandins in conscious rats. The two inhibito rs do not seem to interact endogenously for the inhibition of acid sec retion. While endogenous somatostatin exerts a tonic inhibitory effect on both basal and pentagastrin-simulated acid secretion, prostaglandi ns augment basal acid secretion only.