Somatostatin is an agonist and noncompetitive antagonist of gastrin in oxyntic cell function

Somatostatin inhibits gastric acid secretion in vivo by effects on oxyntic cells which may be indirect. Using quantitative cytochemistry, we have investigated the actions of somatostatin on guinea pig oxyntic cell carbonic anhydrase activity, an index of acid secretion. Cyclic tetradecapeptide somatostatin, in the range of 2.9 X 10(-15) to 2.9 X 10(-10) M, stimulated oxyntic cell carbonic anhydrase activity in sections of guinea pig gastric fundus with a linear dose-response between 2.9 X 10(-14) and 2.9 x 10(-11) M. The maximal response to somatostatin was 50% of that to gastrin. Gastrin stimulated oxyntic cell carbonic anhydrase in the dose range of 2.3 X 10(-15) to 2.3 X 10(-11) M. The addition of 2.9 x 10(-13) M somatostatin caused an inhibition of 38-75% of the carbonic anhydrase activity stimulated by various concentrations of gastrin. The addition of 2.3 X 10(-13) M gastrin (which caused 79% of maximal carbonic anhydrase activation), to each dose of somatostatin from 2.9 X 10(-15) to 2.9 X 10(-10) M did not alter the action of somatostatin, and the action of gastrin was reduced to that observed with somatostatin alone. The data indicate noncompetitive inhibition between somatostatin and gastrin. Thus, somatostatin is an intrinsic, albeit weak, stimulator of gastric oxyntic cell carbonic anhydrase activity, and despite this, is a noncompetitive antagonist of the action of gastrin. Gastrin is an agonist and noncompetitive antagonist of the action of somatostatin.