G protein signalling pathways in myometrium: affecting the balance between contraction and relaxation

Abstract

Heterotrimeric G proteins are actively involved in intracellular signalling in the myometrium and play important roles in regulating myometrial contraction and relaxation. Increases in intracellular calcium can be induced by agents that stimulate uterine contractions. In a number of instances, these increases in intracellular calcium are attributed to stimulation of phospholipase C by either G alpha or G betagamma subunits as a result of activation of G protein-coupled plasma membrane receptors. This mechanism also stimulates calcium entry through calcium release-activated channels, either directly or indirectly. Thus, while phospholipase C can be activated by other pathways and calcium can enter myometrial cells through other channels, G proteins play a major role in these processes. Similarly, activation of protein kinase A and protein kinase C are consequences of G protein activation. Protein kinase A and protein kinase C exert a number of regulatory influences on phospholipase C, ion channel activity and other processes in the myometrium. The mitogen-activated protein kinase pathway can also be activated directly or indirectly by the action of G proteins in myometrium. Responsiveness to G proteins can be altered during pregnancy and depends on the relative expression of all of the components of the signalling pathways involved. The balance between G protein-mediated stimulatory and inhibitory signalling pathways has important consequences for the control of myometrial contractile activity.