Cholinergic regulation of PP release is mediated through muscarinic M1-receptors.

The effects of the selective muscarinic M1-receptor antagonist pirenzepine and the nonselective muscarinic antagonist atropine on bombesin- and peptone-stimulated release of pancreatic polypeptide (PP) were studied in healthy subjects. To exclude any effect of changes in intraduodenal pH continuous intragastric titration was performed during all tests. Both pirenzepine (i.v. bolus 0.6 mg/kg) and atropine (i.v. bolus 15 micrograms/kg, followed by an infusion of 5 micrograms/kg.h) significantly reduced peptone-induced integrated mean rise of plasma PP from 28 +/- 5 to 8 +/- 4 and -2 +/- 5 pmol/l, respectively (n = 4). Both drugs also reduced bombesin-induced rise of plasma PP in all 4 subjects, from 27 +/- 12 to 6 +/- 4 and 7 +/- 1 pmol/l (0.05 less than p less than 0.1). It is concluded that cholinergic regulation of PP release is mediated mainly through muscarinic M1-receptors.