Kinetics of atropine inhibition of pentagastrin-stimulated H+, electrolyte, and pepsin secretion in the dog

Abstract

The effects of atropine on pentagastrin-stimulated gastric secretion of water, H, Cl, Na, K, and pepsin were determined by kinetic analysis of dose-response studies in 5 dogs with esophagostomy and gastric cannula. First a dose-response study was done using 7 doses of pentagastrin (1-6 mug/kg hr), each dose given by I.V. infusion for 4 hr at a separate time. The same series of doses was used with atropine sulfate 10 mug/kg hr as background. Atropine inhibited pentagastrin-stimulated secretion competively with a dose ratio change of 20. In a third set of studies pentagastrin was infused alone for 4 hrs in the dose of 1.5 mug/kg hr and then with each of 7 doses of atropine (0.625-40 mug/kg hr), each dose used separately. Atropine competitively inhibited water, H, Cl, and K secretion, with Ki (dose of atropine giving 50% inhibition) of 1.0 mug/kg hr. Pepsin secretion was much more strongly inhibited than acid secretion by atropine with Ki 0.27 mug/kg hr and the inhibition was uncompetitive. Calculated maximal inhibition of H+ secretion by atropine was 89% and of pepsin 95%. Furthermore the shape of the response to pentagastrin was altered by atropine so that the peak response was delayed to the third and fourth hour of pentagastrin infusion.