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Atypical regulation of hepatic adenylyl cyclase and adrenergic receptors during a critical developmental period: agonists evoke supersensitivity accompanied by failure of receptor down-regulation.

Publication ,  Journal Article
Thai, L; Galluzzo, JM; McCook, EC; Seidler, FJ; Slotkin, TA
Published in: Pediatr Res
April 1996

Ordinarily, beta-adrenergic receptors and responses linked to the receptors increase with development but in the liver, beta-receptors are higher in the fetus and neonate than in adulthood. We examined how hepatic beta-receptor signaling mediated through adenylyl cyclase is regulated in rats of different ages. In each case, animals were pretreated with isoproterenol for 4 d, and on the 5th d, hepatic membrane preparations were examined for adenylyl cyclase activity and receptor binding capabilities. Uniquely in 6-d-old animals, the cyclase response to isoproterenol was enhanced by chronic pretreatment, caused by heterologous sensitization mediated through effects on total catalytic activity (increased response to forskolin-Mn2+) and on G-protein coupling (enhanced effect of fluoride and increased GTP dependence of basal activity). Isoproterenol pretreatment failed to cause beta-receptor down-regulation in 6-d-old animals, but by 15 d of age, down-regulation was detected along with slight desensitization of the cyclase response. However, at 25 d, neither effect was present. In adulthood, repeated isoproterenol administration failed to cause cyclase desensitization but did reduce beta-receptor numbers; the loss of receptors was still unusual in that beta-receptor down-regulation could be achieved with either isoproterenol or with methoxamine, an alpha-receptor agonist. The results indicate that, early in development, hepatic beta-receptor-mediated responses are enhanced, not desensitized, after chronic stimulation. These effects would foster responsiveness of hepatic gluconeogenesis in the face of the massive adrenergic stimulation associated with the transition from fetal to neonatal life. In adulthood, when receptor numbers are far lower than in the neonate, the inability to desensitize the signaling cascade despite receptor down-regulation would serve to maintain the response to catecholamines.

Duke Scholars

Published In

Pediatr Res

DOI

ISSN

0031-3998

Publication Date

April 1996

Volume

39

Issue

4 Pt 1

Start / End Page

697 / 707

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Pediatrics
  • Myocardium
  • Male
  • Liver
  • Isoproterenol
  • Heart
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Thai, L., Galluzzo, J. M., McCook, E. C., Seidler, F. J., & Slotkin, T. A. (1996). Atypical regulation of hepatic adenylyl cyclase and adrenergic receptors during a critical developmental period: agonists evoke supersensitivity accompanied by failure of receptor down-regulation. Pediatr Res, 39(4 Pt 1), 697–707. https://doi.org/10.1203/00006450-199604000-00023
Thai, L., J. M. Galluzzo, E. C. McCook, F. J. Seidler, and T. A. Slotkin. “Atypical regulation of hepatic adenylyl cyclase and adrenergic receptors during a critical developmental period: agonists evoke supersensitivity accompanied by failure of receptor down-regulation.Pediatr Res 39, no. 4 Pt 1 (April 1996): 697–707. https://doi.org/10.1203/00006450-199604000-00023.

Published In

Pediatr Res

DOI

ISSN

0031-3998

Publication Date

April 1996

Volume

39

Issue

4 Pt 1

Start / End Page

697 / 707

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Pediatrics
  • Myocardium
  • Male
  • Liver
  • Isoproterenol
  • Heart