Beta-adrenoceptor control of G protein function in the neonate: determinant of desensitization or sensitization.
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.
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- Terbutaline
- Subcellular Fractions
- Receptors, Adrenergic, beta-2
- Receptors, Adrenergic, beta-1
- Receptors, Adrenergic, beta
- Rats, Sprague-Dawley
- Rats
- Pregnancy
- Physiology
- Pertussis Toxin
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
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