The rat uterus is composed of two separate smooth muscle layers: an outer longitudinal and an inner circular layer. Responses to a variety of pharmacological agents differ between the two layers. The longitudinal layer demonstrates greater sensitivity to isoproterenol, which results, in part, from a threefold greater maximum increase in isoproterenol-stimulated adenylyl cyclase activity. Because of the greater importance of the (3-adrenergic/cAMP relaxation pathway in the longitudinal muscle layer, and because of the very low basal, GTP-, or isoproterenol-stimulated adenylyl cyclase activity in the inner circular layer, we limited our investigation of adenylyl cyclase isoforms to the longitudinal muscle layer.
A potential mechanism for postreceptor changes in ad-enylyl cyclase activity during pregnancy and parturition is an alteration in expression of adenylyl cyclase isoforms. Because regulation of activity of these isoforms differs, an increase or decrease in the expression of a single isoform could result in a global alteration of adenylyl cyclase activity. For example, (З7 subunits liberated from heterotri-meric G proteins inhibit adenylyl cyclase type I, stimulate type II, and are without effects on type III. If expression of adenylyl cyclase isoform II, but not type III, decreased at the end of pregnancy, and if adenylyl cyclase isoform II is a predominant isoform in myometrium, then activation of G proteins and release of (З7 subunits would produce less stimulation of total adenylyl cyclase, leading to decreased cAMP production, decreased uterine relaxation, loss of uterine quiescence, and initiation of labor. asthma inhalers
In summary, we found that fresh uterus and cultured, immortalized myometrial cells from late-gestation rats express an identical pattern of mRNA for adenylyl cyclase isoforms. The presence of these multiple isoforms of ad-enylyl cyclase may provide myometrial cells with flexibility to alter uterine contractility in response to external influences.