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Ontogeny of G-protein expression: control by beta-adrenoceptors.

Publication ,  Journal Article
Zeiders, JL; Seidler, FJ; Slotkin, TA
Published in: Brain Res Dev Brain Res
April 14, 2000

Cardiac cell homeostasis is maintained in the face of excessive beta-adrenoceptor stimulation through the process of desensitization. Desensitization is not an inherent property of these cells but rather is acquired during development; neonates given beta-agonists actually show heterologous sensitization, involving changes in the expression and catalytic activity of adenylyl cyclase (AC) as well as an increased receptor/G-protein coupling. The current study examines the role of specific G-protein components, G(s)alpha and G(i)alpha, in the ontogeny of beta-adrenoceptor responses and in the transition from agonist-induced sensitization to desensitization. Between postnatal days (PN) 6 and 15 there was a significant decrease in the 52 kDa isoform of G(s)alpha with no accompanying change of the 45 kDa form; over the same period, G(i)alpha3 also declined substantially. In contrast, the 45 kDa isoform of G(s)alpha and G(i)alpha1,2 remained fairly constant over the same period and fluoride-stimulated AC activity increased. Treatment with isoproterenol on PN2-5 did not result in any significant changes in G(s)alpha expression but robustly decreased G(i)alpha1,2. These changes were accompanied by heterologous sensitization of AC activity at the level of AC itself, evidenced by equivalent increases in the enzymatic response to fluoride and forskolin-Mn2+. Isoproterenol given to older animals (PN11-14) also caused specific loss of G(i) protein, in this case targeting G(i)alpha3, whereas G(s)alpha again was unchanged; in contrast to the younger group, the older animals displayed heterologous desensitization of AC at the level of G-protein function (specific loss of the fluoride response). These results indicate that the normal ontogenetic increase of cardiac beta-adrenoceptor coupling to AC is not dependent on the absolute amount of G-proteins, nor on the relative balance of stimulatory (G(s)) and inhibitory (G(i)) subunits. However, the ability of receptor stimulation to downregulate G(i)alpha1,2, an event which is specific to immature cardiac cells, is likely to be an important component of the resistance of the fetal/neonatal heart to agonist-induced desensitization and hypertrophy. The maintenance of cardiac beta-adrenoceptor signaling in the face of intense stimulation is likely to play an important role in the physiologic adaptations necessary to the perinatal transition.

Duke Scholars

Published In

Brain Res Dev Brain Res

DOI

ISSN

0165-3806

Publication Date

April 14, 2000

Volume

120

Issue

2

Start / End Page

125 / 134

Location

Netherlands

Related Subject Headings

  • Sympatholytics
  • Sympathetic Fibers, Postganglionic
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Oxidopamine
  • Neurology & Neurosurgery
  • Myocardium
  • Male
 

Citation

APA
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ICMJE
MLA
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Zeiders, J. L., Seidler, F. J., & Slotkin, T. A. (2000). Ontogeny of G-protein expression: control by beta-adrenoceptors. Brain Res Dev Brain Res, 120(2), 125–134. https://doi.org/10.1016/s0165-3806(99)00188-1
Zeiders, J. L., F. J. Seidler, and T. A. Slotkin. “Ontogeny of G-protein expression: control by beta-adrenoceptors.Brain Res Dev Brain Res 120, no. 2 (April 14, 2000): 125–34. https://doi.org/10.1016/s0165-3806(99)00188-1.
Zeiders JL, Seidler FJ, Slotkin TA. Ontogeny of G-protein expression: control by beta-adrenoceptors. Brain Res Dev Brain Res. 2000 Apr 14;120(2):125–34.
Zeiders, J. L., et al. “Ontogeny of G-protein expression: control by beta-adrenoceptors.Brain Res Dev Brain Res, vol. 120, no. 2, Apr. 2000, pp. 125–34. Pubmed, doi:10.1016/s0165-3806(99)00188-1.
Zeiders JL, Seidler FJ, Slotkin TA. Ontogeny of G-protein expression: control by beta-adrenoceptors. Brain Res Dev Brain Res. 2000 Apr 14;120(2):125–134.
Journal cover image

Published In

Brain Res Dev Brain Res

DOI

ISSN

0165-3806

Publication Date

April 14, 2000

Volume

120

Issue

2

Start / End Page

125 / 134

Location

Netherlands

Related Subject Headings

  • Sympatholytics
  • Sympathetic Fibers, Postganglionic
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Oxidopamine
  • Neurology & Neurosurgery
  • Myocardium
  • Male