Differential effect of prostaglandins on gallstone-free and gallstone-containing human gallbladder

Nonsteroidal antiinflammatory drugs, inhibitors of prostaglandin synthesis, have different effects on gallbladder contractility in normal and diseased human gallbladders in vivo. We investigated this differential effect by comparing the effects of prostaglandins PGE2 and PGF2alpha, the thromboxane A2 mimetic U46619, and PGI2 on in vitro contractility in gallstone-free and gallstone-containing human gallbladders. Isometric tension was measured in gallbladder muscle strips mounted in organ baths. EC50 was calculated for each agonist. The rank order of potency in gallstone-free gallbladders was PGE2 > CCK > U46619 > PGF2alpha and in gallstone-containing gallbladders was U46619 > PGE2 > CCK > PGF2alpha. PGI2 produced contraction of gallstone-free gallbladder and relaxation of gallstone-containing gallbladder in the basal state. Further, PGI2 produced no relaxation in gallstone-free muscle strips precontracted with CCK, but significant relaxation in CCK precontracted gallstone-containing strips. PGE2, PGF2alpha, and U46619 are potent contractors of gallstone-free and gallstone-containing gallbladders, whereas PGI2 relaxes only gallstone-containing gallbladders. Since gallbladders containing cholesterol-supersaturated bile produce increased PGI2, this PGI2-induced relaxation may be a determinant of the impaired gallbladder motility of gallstone disease.