Expression of beta-adrenergic receptor kinase subtypes in the pregnant rat myometrium.

Abstract

This study tested the hypothesis that the increase in uterine tachyphylaxis to beta-adrenergic stimulation during pregnancy is associated with increased expression of the beta-adrenergic receptor-inactivating protein kinases. Messenger ribonucleic acid was isolated from snap-frozen myometrium collected from nonpregnant and pregnant rats ranging from 10 to 22 days of gestation. Autoradiographic analysis of beta-adrenergic receptor-inactivating protein kinase messenger ribonucleic acid expression was performed after hybridization with specific complementary deoxyribonucleic acid probes for types 1 and 2 beta-adrenergic receptor-inactivating protein kinases. Probe-specific hybridization was normalized for ribosomal ribonucleic acid detected with methylene blue. Protein expression was detected by Western analysis with use of specific polyclonal antibodies. Myometrial beta-adrenergic receptor-inactivating protein kinase type 2 messenger ribonucleic acid and protein levels increased during the course of pregnancy and in postpartum day 1. In contrast, type 1 levels remained unchanged during the same period. Estrogen treatment resulted in a modest 20% decrease in messenger ribonucleic acid levels of both subtypes. This effect was reversed with progesterone treatment. These results suggest that the myometrium undergoes a functional remodeling late in pregnancy to a state promoting myometrial contractions. The increased myometrial expression of type 2 beta-adrenergic receptor-inactivating kinase may explain the decreased effectiveness of beta 2-adrenergic receptor-mediated contraction inhibition at the end of pregnancy and labor.