CARBACHOL STIMULATION OF GASTRIC-ACID SECRETION AND ITS EFFECTS ON THE PARIETAL-CELL

1 The acid secretagogue effect of gastrin is mainly mediated by the re lease of enterochromaffin-like (ECL) cell histamine, but the mechanism of muscarinic stimulation of acid secretion remains unclear. The resu lts of studying aminopyrine uptake in isolated parietal cells, and his tamine release in isolated ECL cells suggest that muscarinic agents ma y act both directly on the parietal cell and indirectly via histamine release from ECL cells. 2 We examined parietal and ECL cell responses to the muscarinic agent carbamylcholine (carbachol) in conscious rats and in rat isolated vascularly perfused stomachs. 3 Intravenous carbac hol stimulated acid secretion in conscious gastric fistula rats and in creased H+K+ ATPase mRNA abundance, indicating activation of parietal cells. In these experiments there was no increase in portal venous his tamine, or in oxyntic mucosal histidine decarboxylase (HDC) enzyme act ivity and HDC mRNA abundance. 4 In rat isolated stomachs stimulated wi th carbachol in the dose range 10 nM-1 mM only the 1 mu M concentratio n increased venous histamine significantly. 5 We concluded that the mu scarinic agent carbachol stimulates acid secretion and H+K+ ATPase mRN A in vivo by a direct effect on the parietal cell, that does not depen d on the release of ECL cell histamine.