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

Terbutaline (Ter), a beta (2)-adrenergic agonist used in preterm labor, stimulates fetal beta -adrenoceptors (beta -ARs). We administered Ter to pregnant rats on gestational days 17-20 and examined beta -ARs and adenylyl cyclase (AC) signaling in heart and liver. Ter produced less downregulation of cardiac beta -ARs than in adults, despite a higher proportion of the beta (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 beta -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 beta -ARs, in keeping with the predominance of the beta (2)-subtype; hepatic receptor downregulation was equivalent in fetus and adult. Nevertheless, there was still no desensitization of beta -AR-mediated AC responses and again AC was induced. Our results indicate that, unlike in the adult, fetal beta -AR signaling is not desensitized by beta -agonists and, in fact, displays heterologous sensitization, thus sustaining responses during parturition. At the same time, the inability to desensitize beta -AR AC responses may lead to disruption of cardiac, hepatic, or neural cell development as a consequence of tocolytic therapy with beta -agonists.