beta-Adrenoceptor-mediated cell signaling in the neonatal heart and liver:responses to terbutaline

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.