FIGURE 21-8 G-protein-coupled receptor signal transduction pathways. A. Receptors coupled to heterotrimeric guanosine-triphosphate (GTP)-binding proteins (G proteins) are integral transmembrane proteins tl13t transduce extracellular signals to the cell interior. G-protein-coupled receptors exhibit a common structural motif consisting of seven membrane-spanning regions. B. Receptor occupation promotes interaction between the receptor and the G protein on the interior surface of the membrane. This induces an exchange of guanosine diphosphate (GOP) for GTP on the G protein Q subunit and dissociation of the Q subunit from the 31 heterodimer. Depending on its isoform, the GTP-Q subunit complex mediates intracellular signaling either indirectly by acting on effector molecules such as adenylyl cyclase (AC) or phospholipase C (PLC), or directly by regulating ion channel or kinase function. cAMP cyclic adenosine monophosphate; DAG diacylglycerol; IP3 inositol triphosphate.
levels of cAMP, and myometrial cell relaxation. The rate-lim iting factor is likely the number of receptors expressed and the level of adenylyl cyclase expression. Agents binding to these receptors have been used for tocolysis of preterm labor and include ritodrine and terbutaline (Chap. 42, p. 826).
LH and hCG hormones share the same receptor, and this smooth muscle and blood vessels (Ziecik, 1992). Levels of myometrial LH-hCG receptors during pregnancy are greater before than during labor. Chorionic gonadotropin acts to acti vate adenylyl cyclase by way of a plasma membrane receptor
G's-linked system. This lessens contraction frequency and force and lowers the number of tissue-speciic myometrial cell gap junctions (Ambrus, 1994; Eta, 1994). hus, high circulating levels of hCG may be one mechanism of uterine quiescence.
In the mouse, variations in FSH-receptor density also regulate myometrial contractile activity (Stilley, 2016).
four G-protein-coupled receptors. Speciically, prostaglandin
E receptors 1 through 4 (EP ,-EP 4) are expressed in the myo metrium during pregnancy and with labor onset (Astle, 2005;
Leonhardt, 2003). EP2 and EP4 act through G's to raise cAMP levels and maintain myometrial cell quiescence but switch to a G'q/1i1 calcium-activating pathway during labor (Kandola, 2014). EP] and EP3 receptors act through G'q and G'i to aug ment intracellular Ca2+ and contractility.
he peptide hormone relaxin binds to the G-protein-coupled receptor named reaxin amiy peptide receptor 1 (FP 1). Binding activates adenylyl cyclase in uterine smooth muscle cells. Adenylyl cyclase in turn prevents increased intracellular Ca2+ and thus promotes uterine quiescence (Downing, 1993; Meera, 1995). There are two separate human relaxin genes, designated HI and H2. Of these, HI is primarily expressed in the decidua, trophoblast, and prostate, whereas H2 is primarily expressed in the corpus luteum. Relaxin in plasma of pregnant women is believed to originate exclusively from corpus luteum secretion. Plasma levels peak at approximately 1 ng/mL between 8 and 12 weeks' gestation. Thereater, they decline to lower levels that persist until term.