Pregnancy suppresses G protein coupling to phosphoinositide hydrolysis in guinea pig myometrium

The regulatory factors controlling uterine contractile activity during pregnancy remain unclear, although pathways modulating intracellular Ca2+ and prostaglandin production play an important role. Because excitatory hormones raise myometrial Ca2+ levels and prostaglandin output through increasing phosphoinositide hydrolysis, regulation of G protein coupling to phospholipase C activation could be a key site for control. To measure the functional activity of this signaling pathway, we measured formation of [3H]inositol phosphates from prelabeled guinea pig myometrial membranes in response to G protein activation by guanosine 5'-[gamma-thio]triphosphate (GTP gamma S) and fluoride. Although these agents stimulated a three- to fivefold increase in phosphoinositide phospholipase C activity in nonpregnant myometrium, at 46-47, 53-60, and 66-69 days of pregnancy (full term 67 +/- 2 days) this response fell by 43-83%. Moreover, the half-maximal effective dose (ED50) for GTP gamma S action was increased from 8.11 ...