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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Auman, JT; Seidler, FJ; Slotkin, TA

Published Date

  • October 1, 2001

Published In

Volume / Issue

  • 281 / 4

Start / End Page

  • R1079 - R1089

PubMed ID

  • 11557613

Pubmed Central ID

  • 11557613

International Standard Serial Number (ISSN)

  • 0363-6119

Digital Object Identifier (DOI)

  • 10.1152/ajpregu.2001.281.4.R1079

Language

  • eng

Conference Location

  • United States