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Beta-adrenoceptor-mediated cell signaling in the neonatal heart and liver: responses to terbutaline.

Publication ,  Journal Article
Auman, JT; Seidler, FJ; Tate, CA; Slotkin, TA
Published in: Am J Physiol Regul Integr Comp Physiol
December 2001

Terbutaline, a beta(2)-adrenoceptor (beta(2)-AR) agonist, is a widely used tocolytic that also crosses the placenta to stimulate fetal beta-ARs. The current study examines the effects of terbutaline administered to neonatal 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-ARs, with a much greater effect in the liver. Despite the reduction in cardiac beta-ARs, receptor desensitization was absent as evidenced by the maintained ability of isoproterenol to stimulate adenylyl cyclase (AC) in membrane preparations. The underlying mechanism was dissected by using stimulants that operate at different points in the AC signaling pathway, NaF, forskolin, and Mn(2+). When administered in the early neonatal period, terbutaline failed to evoke any changes in cardiac AC activity; however, treatment on PN 11-14 evoked heterologous sensitization downstream from the receptor, evidenced by increases in the response to NaF and forskolin. In the liver, neonatal terbutaline administration elicited a small (approximately equal to 10%) decrease in the AC response to isoproterenol, an effect much smaller than the downregulation of beta-ARs (>40%). In this tissue, desensitization was again offset by heterologous sensitization of AC signaling. These results indicate that, in the developing organism, beta-AR-mediated cell signaling responses are maintained in the face of receptor downregulation through heterologous induction of downstream signaling elements. These unique responses serve to sustain beta-AR signaling in the perinatal period.

Duke Scholars

Published In

Am J Physiol Regul Integr Comp Physiol

DOI

ISSN

0363-6119

Publication Date

December 2001

Volume

281

Issue

6

Start / End Page

R1895 / R1901

Location

United States

Related Subject Headings

  • Terbutaline
  • Sodium Fluoride
  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Physiology
  • Organ Size
  • Membrane Proteins
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
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Auman, J. T., Seidler, F. J., Tate, C. A., & Slotkin, T. A. (2001). Beta-adrenoceptor-mediated cell signaling in the neonatal heart and liver: responses to terbutaline. Am J Physiol Regul Integr Comp Physiol, 281(6), R1895–R1901. https://doi.org/10.1152/ajpregu.2001.281.6.R1895
Auman, J. T., F. J. Seidler, C. A. Tate, and T. A. Slotkin. “Beta-adrenoceptor-mediated cell signaling in the neonatal heart and liver: responses to terbutaline.Am J Physiol Regul Integr Comp Physiol 281, no. 6 (December 2001): R1895–1901. https://doi.org/10.1152/ajpregu.2001.281.6.R1895.
Auman JT, Seidler FJ, Tate CA, Slotkin TA. Beta-adrenoceptor-mediated cell signaling in the neonatal heart and liver: responses to terbutaline. Am J Physiol Regul Integr Comp Physiol. 2001 Dec;281(6):R1895–901.
Auman, J. T., et al. “Beta-adrenoceptor-mediated cell signaling in the neonatal heart and liver: responses to terbutaline.Am J Physiol Regul Integr Comp Physiol, vol. 281, no. 6, Dec. 2001, pp. R1895–901. Pubmed, doi:10.1152/ajpregu.2001.281.6.R1895.
Auman JT, Seidler FJ, Tate CA, Slotkin TA. Beta-adrenoceptor-mediated cell signaling in the neonatal heart and liver: responses to terbutaline. Am J Physiol Regul Integr Comp Physiol. 2001 Dec;281(6):R1895–R1901.

Published In

Am J Physiol Regul Integr Comp Physiol

DOI

ISSN

0363-6119

Publication Date

December 2001

Volume

281

Issue

6

Start / End Page

R1895 / R1901

Location

United States

Related Subject Headings

  • Terbutaline
  • Sodium Fluoride
  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Physiology
  • Organ Size
  • Membrane Proteins
  • Male