Luminal cholecystokinin and gastrin cause gallbladder contraction.

Cholecystokinin-8 placed in the gallbladder lumen causes gallbladder contraction by a neurally mediated, tetrodotoxin-sensitive mechanism. We wished to determine whether other cholecystokinin-like peptides in the gallbladder lumen cause contraction and whether this response is inhibited by cholecystokinin-receptor antagonists. In this study, we measured gallbladder contraction induced by cholecystokinin-like peptides or by hepatic bile placed in the gallbladder lumen. Isolated gallbladders were suspended in an organ bath while luminal hormones were infused. Gallbladder contraction was measured by continuous monitoring of luminal pressure. Cholecystokinin-8, cholecystokinin-5, and gastrin-17 caused dose-related gallbladder contraction with similar potency when placed in the lumen. Each stimulated 70-80% maximal contraction at a luminal concentration of 10(-6) M. Cholecystokinin-receptor antagonists CR1409 and loxiglumide partially inhibited contraction caused by luminal cholecystokinin-8. Bile from fed animals, but not from fasted animals, stimulated gallbladder contraction to 36 +/- 4% of maximal when placed in the gallbladder lumen. We conclude that cholecystokinin and gastrin peptides in the gallbladder lumen cause contraction. This may be mediated through receptors of the cholecystokinin-B type, possibly on intrinsic nerves. Bile from fed animals also contains substances that stimulate gallbladder contraction when bile is placed in the gallbladder lumen. These findings suggest intrinsic nerves participate in the postprandial gallbladder response to cholecystokinin.