Mechanisms of gallbladder hypomotility in pregnant guinea pigs

Background & Aims: Gallbladder muscle contraction becomes impaired during p regnancy. This study was designed to investigate the mechanisms of gallblad der hypomotility induced by pregnancy in guinea pigs. Methods: Gallbladder muscle cells were obtained by enzymatic digestion. Cell contraction was exp ressed as percent shortening of initial control cell length. Results: Contr action induced by cholecystokinin (CCK)-8 or guanosine 5'-O-(3-thiotriphosp hate) (GTP gamma S) was reduced in muscle cells from pregnant guinea pigs. The response to KCI or D-myo-inositol 1,4,5-trisphosphate was not different between controls and pregnant animals. These findings suggest that impaire d contraction in pregnancy might be caused by defective G protein activatio n. The function and content of G proteins were examined by using [S-35]GTP gamma S binding and G protein subunit quantitation. In female controls, CCK -8 at 1 mu mol/L caused increased [S-35]GTP gamma S binding to G alpha i3 b ut not to G alpha q/11, G alpha i1-2, or G alpha s. GTP gamma S binding to G alpha i3 induced by CCK-8 was reduced in gallbladder muscle from pregnant guinea pigs. Measurements of basal G proteins showed that the content of G alpha i3 was significantly lower and the G alpha s content was higher in m uscles from pregnant guinea pigs than in controls. Conclusions: pregnancy m ay cause down-regulation of contractile G proteins such as G alpha i3 and u p-regulation of G alpha s that mediates relaxation, resulting in impaired g allbladder muscle contraction.