Mechanisms of gallbladder hypomotility in pregnant guinea pigs

BACKGROUND & AIMS: Gallbladder muscle contraction becomes impaired during pregnancy. This study was designed to investigate the mechanisms of gallbladder hypomotility induced by pregnancy in guinea pigs. METHODS: Gallbladder muscle cells were obtained by enzymatic digestion. Cell contraction was expressed as percent shortening of initial control cell length. RESULTS: Contraction induced by cholecystokinin (CCK)-8 or guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) was reduced in muscle cells from pregnant guinea pigs. The response to KCl or D-myo-inositol 1,4, 5-trisphosphate was not different between controls and pregnant animals. These findings suggest that impaired contraction in pregnancy might be caused by defective G protein activation. The function and content of G proteins were examined by using [35S]GTPgammaS binding and G protein subunit quantitation. In female controls, CCK-8 at 1 micromol/L caused increased [35S]GTPgammaS binding to Galphai3 but not to Galphaq/11, Galphai1-2, or Galphas. GTPgammaS binding to Galphai3 induced by CCK-8 was reduced in gallbladder muscle from pregnant guinea pigs. Measurements of basal G proteins showed that the content of Galphai3 was significantly lower and the Galphas content was higher in muscles from pregnant guinea pigs than in controls. CONCLUSIONS: Pregnancy may cause down-regulation of contractile G proteins such as Galphai3 and up-regulation of Galphas that mediates relaxation, resulting in impaired gallbladder muscle contraction.