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Beta-adrenoceptor control of G protein function in the neonate: determinant of desensitization or sensitization.

Publication ,  Journal Article
Auman, JT; Seidler, FJ; Slotkin, TA
Published in: Am J Physiol Regul Integr Comp Physiol
November 2002

Neonatal beta-adrenoceptors (beta-ARs) are resistant to agonist-induced desensitization. We examined the functioning of G(i) and G(s) after repeated administration of beta-AR agonists to newborn rats. Isoproterenol (beta(1)/beta(2) agonist) obtunded G(i) function in the heart but not the liver; in contrast, terbutaline, a beta(2)-selective agonist, enhanced G(i) function. Isoproterenol, but not terbutaline, increased membrane-associated G((s)alpha), which would enhance receptor function. In addition, isoproterenol increased and terbutaline maintained the proportion of the short-splice (S) variant of G((s)alpha) in the membrane fraction; G((s)alpha)S is functionally more active than the long-splice variant. Either isoproterenol or terbutaline treatment increased G((s)alpha) in the cytosolic fraction, a characteristic usually associated with desensitization in the adult. Decreased G(i) activity, coupled with increased membrane-associated G((s)alpha) concentrations and maintenance or increases in membrane G((s)alpha)S, provide strong evidence that unique effects on G protein function underlie the ability of the immature organism to sustain beta-AR cell signaling in the face of excessive or prolonged stimulation; these mechanisms also contribute to tissue selectivity of the effects of beta-agonists with divergent potencies toward different beta-AR subtypes.

Duke Scholars

Published In

Am J Physiol Regul Integr Comp Physiol

DOI

ISSN

0363-6119

Publication Date

November 2002

Volume

283

Issue

5

Start / End Page

R1236 / R1244

Location

United States

Related Subject Headings

  • Terbutaline
  • Subcellular Fractions
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Physiology
  • Pertussis Toxin
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Auman, J. T., Seidler, F. J., & Slotkin, T. A. (2002). Beta-adrenoceptor control of G protein function in the neonate: determinant of desensitization or sensitization. Am J Physiol Regul Integr Comp Physiol, 283(5), R1236–R1244. https://doi.org/10.1152/ajpregu.00409.2002
Auman, J. T., F. J. Seidler, and T. A. Slotkin. “Beta-adrenoceptor control of G protein function in the neonate: determinant of desensitization or sensitization.Am J Physiol Regul Integr Comp Physiol 283, no. 5 (November 2002): R1236–44. https://doi.org/10.1152/ajpregu.00409.2002.
Auman JT, Seidler FJ, Slotkin TA. Beta-adrenoceptor control of G protein function in the neonate: determinant of desensitization or sensitization. Am J Physiol Regul Integr Comp Physiol. 2002 Nov;283(5):R1236–44.
Auman, J. T., et al. “Beta-adrenoceptor control of G protein function in the neonate: determinant of desensitization or sensitization.Am J Physiol Regul Integr Comp Physiol, vol. 283, no. 5, Nov. 2002, pp. R1236–44. Pubmed, doi:10.1152/ajpregu.00409.2002.
Auman JT, Seidler FJ, Slotkin TA. Beta-adrenoceptor control of G protein function in the neonate: determinant of desensitization or sensitization. Am J Physiol Regul Integr Comp Physiol. 2002 Nov;283(5):R1236–R1244.

Published In

Am J Physiol Regul Integr Comp Physiol

DOI

ISSN

0363-6119

Publication Date

November 2002

Volume

283

Issue

5

Start / End Page

R1236 / R1244

Location

United States

Related Subject Headings

  • Terbutaline
  • Subcellular Fractions
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Physiology
  • Pertussis Toxin