Mechanisms of gallbladder hypomotility in pregnant guinea pigs

Gallbladder muscle contraction becomes impaired during pregnancy. This study was designed to investigate the mechanisms of gallbladder hypomotility induced by pregnancy in guinea pigs.

Gallbladder muscle cells were obtained by enzymatic digestion. Cell contraction was expressed as percent shortening of initial control cell length.

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.

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.