Pepsinogen release from isolated gastric glands

Abstract

The in vitro release of pepsinogen was studied using a preparation of isolated gastric glands from rabbits. The pepsinogen content of the glands was estimated to be .apprx. 700 U/mg dry wt. Spontaneous release of pepsinogen was < 1% of the total per hour and relatively constant for at least 2 h. Pepsinogen release was stimulated in a dose-dependent manner by both carbachol and isoproterenol. The cholinergic and .beta.-adrenergic stimulation was selectively inhibited by atropine and propranolol, respectively. Removal of external Ca inhibited the responses to both isoproterenol (partially) and carbachol (completely). Several agents including histamine, prostaglandin (E2) and synthetic secretin, did not stimulate pepsinogen release. However, a crude secretin preparation (Boots) did produce significant stimulation. Dibutyryl cAMP increased pepsinogen release in a dose-dependent manner. Isoproterenol increased the cAMP content of gastric glands and stimulated adneylyl cyclase activity in homogenates. The .beta.-adrenergic stimulation of adenylyl cyclase was selective for a population of gastric cells that was relatively depleted of parietal cells and distinct from the histamine-stimulated adenylyl cyclase activity. Pepsinogen secretion by the gastric chief cell is regulated, in part, by separate cholinergic and .beta.-adrenergic mechanisms and both Ca and cAMP play a role in this regulation.