EFFECTS OF PIRENZEPINE AND ATROPINE ON VAGAL AND CHOLINERGIC GASTRIC-SECRETION AND GASTRIN-RELEASE AND ON HEART-RATE IN THE DOG

Abstract

To characterize and quantitate pathways of stimulation of gastric secretion via vagal excitation induced by 2-deoxy-D-glucose, graded doses of the 2 muscarinic antagonists, atropine and pirenzepine, were used. Studies were performed in 4 conscious gastric fistula dogs with antral vagotomy to eliminate the gastric release component of the vagal response. To further localize the site of action of the antagonists, both were tested against bethanechol, which stimulates secretion at postganglionic sties. Acid and pepsin secretion stimulated by either bethanechol or the vagus were inhibited in a dose-responsive manner by both atropine and pirenzepine, which displayed similar potencies. These data indicate the following: the vagus acts on the gastric fundus solely via muscarinic receptors; the muscarinic receptors controlling gastric secretion are of the high-affinity (M-1) subtype; and the vagus is very sensitive to atropine with D50 < 1.4 nmol/kg. Heart rate was increased up to 120 beats/min above the resting rat by atropine; half-maximal increase was calculated to occur at 10 nmol/kg (ED50). Pirenzepine had a much less potent effect on the heart; the ED50 was 200-300 times greater than that for atropine. Heart rate is evidently affected by a mechanism acting via a muscarinic receptor pathway that has a low affinity for pirenzepine (M-2 receptor subtype).