Effects of atropine and bethanechol on bombesin-stimulated release of pancreatic polypeptide and gastrin in dog

Abstract

In dogs with gastric fistulas, intravenous infusion of graded doses of bombesin gave graded increases in plasma concentrations of pancreatic polypeptide and of gastrin. The maximally effective dose, 500 ng kg−1 h−1, gave a mean peak increase over basal of 240 pM for pancreatic polypeptide and 93 pM for gastrin. Atropine sulfate (0.1 mg kg−1 iv) inhibited the pancreatic polypeptide response to bombesin by 60 ± 13% (P < 0.01) but had no significant effect on the gastrin response. Bethanechol (0.1 mg kg−1 h−1) infused alone resulted in a small but statistically significant increment in plasma gastrin concentration (4.5 ± 0.9 pM, P < 0.01) and a larger increment in plasma pancreatic polypeptide concentration (41.7 ± 6.3 pM, P < 0.01). Bethanechol (0.1 mg kg−1 h−1) given together with bombesin (500 ng kg−1 h−1) had no significant effect on the pancreatic polypeptide response but significantly (P < 0.01) inhibited the gastrin response by 50.1 ± 8.9%. The finding that bethanechol inhibited bombesin-induced gastrin release complements earlier evidence for a cholinergic mechanism of inhibition of gastrin release. The findings of release of pancreatic polypeptide by bethanechol and suppression by atropine of bombesin-induced pancreatic polypeptide release add further evidence regarding cholinergic dependence of PP release. This study shows that bombesin, a known releaser of gastrin, also releases pancreatic polypeptide and that the D50 of bombesin for both of these actions is about 125 ng kg−1 h−1.