AJP - Heart and Circulatory Physiology, Vol 253, Issue 5 1159-H1166, Copyright © 1987 by American Physiological Society
Ischemia- and agonist-induced changes in alpha- and beta-adrenergic receptor traffic in guinea pig hearts
A. S. Maisel, H. J. Motulsky, M. G. Ziegler and P. A. Insel
Department of Medicine, University of California, San Diego.
We have used radioligand binding techniques and subcellular fractionation
to assess whether changes in expression of myocardial alpha 1- and
beta-adrenergic receptors are mediated by a redistribution of receptors
between various membrane fractions. Three fractions were prepared from the
left ventricles of guinea pigs that underwent either 1 h of ischemia or
injection of epinephrine (0.25 mg/kg ip): a crude membrane, a purified
sarcolemma, and a light vesicle fraction. In control animals alpha
1-adrenergic receptors ([3H]prazosin binding) in light vesicles was only
25% of the total alpha 1-receptor density found in sarcolemmal and light
vesicle fractions as compared with 50% for beta-adrenergic receptors
([125I]iodocyanopindolol binding sites). Although ischemia was associated
with a 53% decrease in the number of light vesicle beta-adrenergic
receptors and a 42% increase in the number of sarcolemma beta-receptors (P
less than 0.05), there was no change in the number of light vesicle alpha
1-receptors, even though the number of sarcolemmal alpha 1-receptors
increased 34%. Epinephrine treatment promoted internalization of
beta-adrenergic receptors; sarcolemma beta-receptors decreased 37% and
light vesicle beta-receptors increased 28% (P less than 0.025). For alpha
1-receptors, epinephrine treatment decreased the number of sarcolemmal
receptors 41% (P less than 0.025) but failed to increase the number of
receptors in the light vesicle fraction. The changes in receptor binding to
beta-adrenergic receptors in sarcolemmal fractions were mirrored by
parallel changes in isoproterenol-stimulated adenylate cyclase activity.
These results indicate that alpha 1- and beta-adrenergic receptors may
undergo a different cellular itinerary in guinea pig myocardium.(ABSTRACT
TRUNCATED AT 250 WORDS)
