Modulation of gallbladder contraction by pirenzepine in humans

Objectives : The mechanism(s) by which cholinergic innervation modulates gallbladder contraction are not fully understood. To elucidate the role of muscarinic M 1 receptors in the mediation of gallbladder contraction, we investigated gallbladder volume reduction, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) responses in humans during cephalic and intestinal phases of a meal under M 1 muscarinic receptor blockade with pirenzepine. Methods : In eight healthy subjects, intraduodenal meal- and in seven subjects, sham feeding-induced gallbladder volume reduction was measured by real-time ultrasonography during saline or pirenzepine administration. Plasma CCK and PP were measured by radioimmunoassay. Results : Pirenzepine partially inhibited gallbladder volume reduction in response to an intraduodenal fatty meal. The integrated gallbladder volume reduction over 120 min was 4462 ± 445%.min compared with 6879 ± 279%.min in the saline control group (p < 0.01). Integrated plasma CCK and PP responses were unchanged in the presence of pirenzepine. Pirenzepine abolished sham feeding-induced gallbladder contraction and plasma PP response. Sham feeding with either isotonic saline or pirenzepine infusion did not modify fasting plasma CCK levels. Conclusion : M 1 muscarinic receptors play an important role in the intestinal and cephalic phases of gallbladder contraction. Plasma CCK response to intraduodenal meal is not influenced by M 1 muscarinic receptor blockade with pirenzepine.