Receptors and Signal Transduction in the Myometrium

Abstract

In the myometrium, as in many other smooth muscle preparations, Ca²⁺ and cAMP, the two major intracellular second messengers, exert opposite effects at the level of contractility. The necessity of calcium for uterine contraction has long been recognized, the role of Ca²⁺ being obligatory, whether the stimulus is hormonal or voltage-induced. On the other hand, cAMP has been shown to contribute to uterine relaxion (Hardman 1981, Do Khac et al. 1986b, Diamond 1990). The increase in intracellular Ca²⁺ evoked by stimulatory agonists is considered to originate at least in part from intracellular stores (Van Breemen and Saida 1989; Somlyo and Himpens 1989; Mironneau et al. 1984). In this regard, the phosphoinositide-phospholipase C transducing mechanism that is consistently associated with Ca²⁺-mobilizing receptors (Berridge and Irvine 1984; Berridge 1987) has been demonstrated to be activated by contracting agonists in different myometrial preparations (Marc et al. 1986, 1988; Anwer et al. 1989; Goureau et al. 1990). Additionally, a number of recently reported findings provide satisfactory correlations between the increased generation of inositol phosphates, the ability of inositol 1,4,5-trisphosphate, InsP(1,4,5,)P₃, to release Ca²⁺ from intracellular stores, and the accompanying Ca²⁺-induced uterine contractions (Carsten and Miller 1985; Marc et al. 1988;Kanmuraetal. 1988).