Gallbladder relaxation in patients with pigment and cholesterol stones

Background & Aims: Gallbladders with cholesterol stones show a defective contraction in response to agonists. The aim of this study was to investigate the muscle relaxation of human gallbladders with cholesterol or black pigment gallstones. Methods: Gallbladder relaxation was measured in vitro using muscle strips and single muscle cells. Relaxation was expressed as percent inhibition of either basal active tension in strips or maximal cell contraction induced by diacylglycerol. The production of cyclic nucleotides was determined using a I-125-labeled radioimmunoassay kit. Results: Frequency-dependent relaxation evoked by electrical field stimulation was significantly lower in gallbladders with cholesterol stones than in gallbladders with pigment stones. Relaxation and adenosine 3',5'cyclic monophosphate (cAMP) production induced by isoproterenol, vasoactive intestinal peptide, and forskolin were also significantly decreased in gallbladders with cholesterol stones. However, the relaxation in response to 8-bromo-cAMP, nitric oxide (NO), and the NO donor S-nitroso-N-acetylpenicillamine (SNAP), which circumvent plasma membrane receptors and directly activate intracellular mechanisms, was similar in gallbladders with cholesterol and pigment stones. Guanosine 3',5'-cyclic monophosphate production induced by NO and SNAP was also similar. Conclusions: Human gallbladder muscle from specimens with cholesterol stones show an impaired relaxation and lower cAMP production compared with specimens with pigment stones. The muscle defect(s) responsible for this impairment seem to be in the plasma membranes.