Regulation of fetal cardiac and hepatic beta -adrenoceptors and adenylyl cyclase signaling: terbutaline effects

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710 Terbutaline (Ter), a 2 -adrenergic agonist used in preterm labor, stimulates fetal -adrenoceptors ( -ARs). We administered Ter to pregnant rats on gestational days 17-20 and examined -ARs and adenylyl cyclase (AC) signaling in heart and liver. Ter produced less downregulation of cardiac -ARs than in adults, despite a higher proportion of the 2 -subtype, and failed to elicit desensitization of the receptor-mediated AC response. AC stimulants acting at different points indicated an offsetting of homologous desensitization at the level of the -AR by heterologous sensitization at the level of AC: induction of total AC catalytic activity and a shift in the catalytic profile or AC isoform. In fetal liver, Ter produced downregulation of -ARs, in keeping with the predominance of the 2 -subtype; hepatic receptor downregulation was equivalent in fetus and adult. Nevertheless, there was still no desensitization of -AR-mediated AC responses and again AC was induced. Our results indicate that, unlike in the adult, fetal -AR signaling is not desensitized by -agonists and, in fact, displays heterologous sensitization, thus sustaining responses during parturition. At the same time, the inability to desensitize -AR AC responses may lead to disruption of cardiac, hepatic, or neural cell development as a consequence of tocolytic therapy with -agonists. adenosine 3',5'-cyclic monophosphate; development; heart; liver; preterm labor; tocolysis