Downregulation of Gαq-11 protein expression in guinea pig antral and colonic circular muscle during pregnancy

Pregnancy has an inhibitory effect on motility of the gastrointestinal tract. The present study was designed to examine the mechanisms responsible for antral and colonic hypomotility in pregnant guinea pigs. Circular smooth muscle cells from the antrum and left colon were isolated by enzymatic digestion with collagenase from pregnant and nonpregnant guinea pigs. Contractile responses to agonists were expressed as percent shortening from resting cell length. The function of G proteins in antral and colonic circular smooth muscle was assessed by [S-35]guanosine 5'-O(3-thiotriphosphate) (GTP gamma S) binding induced by CCK-8 and G protein quantitation. The contraction of antral and colonic circular smooth muscle from pregnant guinea pigs was reduced in response to CCK-8 and to GTP gamma S but was normal in response to KC1 and D-myo-inositol 1,4,5-trisphosphate compared with nonpregnant animals. The stimulation of [S-35]GTP gamma S binding to G alpha(q-11) induced by 1 mu M CCK-8 was significantly lower in antral and colonic circular smooth muscle from pregnant guinea pigs than that in controls. Furthermore, Western blot analysis showed a decreased G alpha(q-11) and an increased G,or protein content in both tissues during pregnancy. It is concluded that pregnancy appears to impair gastrointestinal circular smooth muscle contractility by downregulating G proteins such as G alpha(q-11) protein, which mediates muscle contraction, and upregulating G(s)alpha protein, which mediates muscle relaxation.