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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Auman, JT; Seidler, FJ; Slotkin, TA

Published Date

  • November 2002

Published In

Volume / Issue

  • 283 / 5

Start / End Page

  • R1236 - R1244

PubMed ID

  • 12376418

Pubmed Central ID

  • 12376418

International Standard Serial Number (ISSN)

  • 0363-6119

Digital Object Identifier (DOI)

  • 10.1152/ajpregu.00409.2002

Language

  • eng

Conference Location

  • United States