Jt. Auman et al., beta-Adrenoceptor-mediated cell signaling in the neonatal heart and liver:responses to terbutaline, AM J P-REG, 281(6), 2001, pp. R1895-R1901
Citations number
30
Categorie Soggetti
Physiology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Terbutaline, a beta (2)-adrenoceptor (beta (2)-AR) agonist, is a widely use
d tocolytic that also crosses the placenta to stimulate fetal beta -ARs. Th
e current study examines the effects of terbutaline administered to neonata
l rats. Terbutaline (10 mg/kg sc) given on postnatal day (PN) 2-5 or PN 11-
14 elicited significant downregulation of both cardiac and hepatic beta -AR
s, with a much greater effect in the liver. Despite the reduction in cardia
c beta -ARs, receptor desensitization was absent as evidenced by the mainta
ined ability of isoproterenol to stimulate adenylyl cyclase (AC) in membran
e preparations. The underlying mechanism was dissected by using stimulants
that operate at different points in the AC signaling pathway, NaF, forskoli
n, and Mn2+. When administered in the early neonatal period, terbutaline fa
iled to evoke any changes in cardiac AC activity; however, treatment on PN
11-14 evoked heterologous sensitization downstream from the receptor, evide
nced by increases in the response to NaF and forskolin. In the liver, neona
tal terbutaline administration elicited a small (approximate to 10%) decrea
se in the AC response to isoproterenol, an effect much smaller than the dow
nregulation of beta -ARs (>40%). In this tissue, desensitization was again
offset by heterologous sensitization of AC signaling. These results indicat
e that, in the developing organism, beta -AR-mediated cell signaling respon
ses are maintained in the face of receptor downregulation through heterolog
ous induction of downstream signaling elements. These unique responses serv
e to sustain beta -AR signaling in the perinatal period.