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, sti mulates fetal beta -adrenoceptors (beta -ARs). We administered Ter to pregn ant rats on gestational days 17-20 and examined beta -ARs and adenylyl cycl ase (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 A C response. AC stimulants acting at different points indicated an offsettin g of homologous desensitization at the level of the beta -AR by heterologou s sensitization at the level of AC: induction of total AC catalytic activit y and a shift in the catalytic profile or AC isoform. In fetal liver, Ter p roduced downregulation of beta -ARs, in keeping with the predominance of th e beta (2)-subtype; hepatic receptor downregulation was equivalent in fetus and adult. Nevertheless, there was still no desensitization of beta -AR-me diated AC responses and again AC was induced. Our results indicate that, un like in the adult, fetal beta -AR signaling is not desensitized by beta -ag onists and, in fact, displays heterologous sensitization, thus sustaining r esponses during parturition. At the same time, the inability to desensitize beta -AR AC responses may lead to disruption of cardiac, hepatic, or neura l cell development as a consequence of tocolytic therapy with beta -agonist s.