Cholinergic secretory and inhibitory mechanisms in canine pancreatic secretion

Dose-response relationships for pancreatic stimulants and the interactions by atropine were studied in conscious gastric and duodenal fistula dogs. Secretin, caerulein, and bethanechol, the two latter against background secretin, induced similar maximal secretions of water and bicarbonate, and maximal protein outputs with the two latter were not different. Actions of atropine differed according to type and dose of stimulant, dose of atropine, and secretory variable studied. In the dose interval of 10-40 microg x kg(-1) x h(-1), atropine suppressed the secretin-stimulated water and bicarbonate, but these or lower doses enhanced the response to submaximal caerulein. The secretion after 200 microg x kg(-1) x h(-1) or less bethanechol was unaffected by atropine, but the suppressed response to higher bethanechol doses was reversed and enhanced. These findings are compatible with the presence of one ductal secretory process sensitive to cholinergic influence in three ways: one secretory, partly atropine-sensitive, required for submaximal secretin's optimal action; one secretory, stimulated by bethanechol, and atropine-resistant; and one inhibitory, atropine-sensitive, triggered by caerulein (and high doses of bethanechol). Atropine at low doses inhibited the protein output by bethanechol but enhanced the submaximal caerulein response, which again indicates the presence of an inhibitory atropine-sensitive cholinergic principle. It is proposed that pancreatic polypeptide may be the mediator of this inhibition and that vasoactive intestinal polypeptide could be the mediator of the atropine-resistant cholinergic stimulation of water and bicarbonate secretion.