INOSITOL TRISPHOSPHATE RESTORES IMPAIRED HUMAN GALLBLADDER MOTILITY ASSOCIATED WITH CHOLESTEROL STONES

Background: Gallbladder motility is impaired in specimens with cholesterol stones but normal with pigment stones. Methods: Muscle cells obtained from 19 human gallbladders with cholesterol stones and 11 with pigment stones were enzymatically digested and contracted with cholecystokinin octapeptide (CCK-8), acetylcholine, and KCl. Results: Muscle cells from pigment stones had a greater contraction than cells from cholesterol stones. CCK-8-induced contraction was unaffected by calcium-free media but was blocked by strontium. Potassium-evoked contraction was blocked by a calcium-free media and unaffected by strontium. Inositol triphosphate (IP-3)-induced contraction was similar to the contraction caused by CCK-8 in permeable cells from pigment stones but was greater than the response to CCK-8 in cells from cholesterol stones. Conclusions: Muscle cells from gallbladders with cholesterol stones contract less than cells from gallbladders with pigment stones; CCK-8-induced contraction only uses stored calcium; and IP-3 causes contractions of equal magnitude in cells from gallbladders with cholesterol and pigment stones. These abnormalities could result from an impaired receptor activation of the mechanism for IP-3 generation and release of stored calcium. © 1993.