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-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
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