Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

Beta-adrenoceptor control of cardiac adenylyl cyclase during development: agonist pretreatment in the neonate uniquely causes heterologous sensitization, not desensitization.

Publication ,  Journal Article
Giannuzzi, CE; Seidler, FJ; Slotkin, TA
Published in: Brain Res
October 2, 1995

In the adult, increased stimulation of postsynaptic receptor sites produces compensatory desensitization that reduces tissue responsiveness. During development, however, responses in most systems increase with age and with the maturation of neuronal inputs. In the current study, we examined whether agonist-induced desensitization of cardiac beta-adrenergic receptor signaling mediated through adenylyl cyclase could be elicited in 6-, 15- and 25-day-old rats, and in adults. In each case, animals were pretreated with isoproterenol daily for four days preceding the experiment, and on the fifth day, cardiac membrane preparations were examined. Fifteen and 25-day-old animals and adults all exhibited desensitization, as demonstrated by a diminished cyclase response to isoproterenol in vitro. However, in 6-day-old animals, the enzymatic response to isoproterenol was enhanced by chronic pretreatment. Measurements of the G-protein-sensitive component of cyclase (decrement in activity obtained with deletion of GTP from the reaction mixture, stimulatory response to fluoride) indicated heterologous desensitization in the older animals, evidenced by diminished dependence on GTP and reduced response to fluoride; the 6-day-old animals showed enhanced GTP dependence and augmentation of the fluoride response. Uniquely in 6-day-old animals, the total catalytic activity of adenylyl cyclase, measured with forskolin-Mn2+, was markedly elevated by chronic isoproterenol pretreatment, whereas it was unaffected in older animals. These data suggest that regulation of receptor signaling is completely different early in neonatal life. Instead of producing desensitization of responses, agonist exposure promotes receptor signaling by enhancing expression and/or catalytic efficiency of adenylyl cyclase. In older animals, the predominant effect is heterologous desensitization mediated at the level of G-proteins. These developmental differences are likely to be important in the maintenance of tissue responsiveness during the period in which innervation develops, as well as in the ability of neurotrophic input to 'program' the responsiveness of target tissues.

Duke Scholars

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

October 2, 1995

Volume

694

Issue

1-2

Start / End Page

271 / 278

Location

Netherlands

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Neurology & Neurosurgery
  • Myocardium
  • Male
  • Isoproterenol
  • Guanosine Triphosphate
  • GTP-Binding Proteins
  • Fluorides
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Giannuzzi, C. E., Seidler, F. J., & Slotkin, T. A. (1995). Beta-adrenoceptor control of cardiac adenylyl cyclase during development: agonist pretreatment in the neonate uniquely causes heterologous sensitization, not desensitization. Brain Res, 694(1–2), 271–278. https://doi.org/10.1016/0006-8993(95)00781-k
Giannuzzi, C. E., F. J. Seidler, and T. A. Slotkin. “Beta-adrenoceptor control of cardiac adenylyl cyclase during development: agonist pretreatment in the neonate uniquely causes heterologous sensitization, not desensitization.Brain Res 694, no. 1–2 (October 2, 1995): 271–78. https://doi.org/10.1016/0006-8993(95)00781-k.
Giannuzzi, C. E., et al. “Beta-adrenoceptor control of cardiac adenylyl cyclase during development: agonist pretreatment in the neonate uniquely causes heterologous sensitization, not desensitization.Brain Res, vol. 694, no. 1–2, Oct. 1995, pp. 271–78. Pubmed, doi:10.1016/0006-8993(95)00781-k.
Journal cover image

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

October 2, 1995

Volume

694

Issue

1-2

Start / End Page

271 / 278

Location

Netherlands

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Neurology & Neurosurgery
  • Myocardium
  • Male
  • Isoproterenol
  • Guanosine Triphosphate
  • GTP-Binding Proteins
  • Fluorides