AJP - Heart and Circulatory Physiology, Vol 256, Issue 1 275-H281, Copyright © 1989 by American Physiological Society
Beta-adrenergic receptor regulation during hypoxia in intact cultured heart cells
J. D. Marsh and K. A. Sweeney
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Regulation of cardiac beta-adrenergic receptors during hypoxia and ischemia
is an area of active investigation, with some investigators reporting an
increase in sarcolemmal beta-receptor number after ischemia. Previous
studies have been limited by the necessity of examining beta-adrenergic
receptor properties in membrane preparations from hypoxic or ischemic
cardiac tissue and drawing conclusions about receptor localization in
intact tissue from the behavior of a fraction of total receptors in
membrane populations. As an approach to examining beta-receptor properties
under well-defined pathophysiological conditions in intact heart cells, we
studied cell-surface beta-receptors and adenylate cyclase activity in
intact cultured chick embryo ventricular cells under conditions of
controlled hypoxia and reoxygenation. During 2 h of hypoxia (PO2 less than
1.5 Torr) there was a progressive decline in cell surface beta-receptors
from 26 +/- 2 to 10 +/- 6 fmol/mg (P less than 0.003) with no change in
antagonist or agonist affinity. Receptor number recovered fully during 2 h
of reoxygenation. Basal adenosine 3',5'-cyclic monophosphate (cAMP)
production was unchanged, but response to isoproterenol in the absence or
presence of a phosphodiesterase inhibitor decreased to about half of the
response for normoxic cells but fully recovered during reoxygenation in a
pattern similar to that for receptor number. Although [ATP] declined
significantly during hypoxia (from 35 to 25 nmol/mg), the decline in [GTP]
was marginal (4.3 to 3.9 nmol/mg), making it unlikely that substrate for
guanine nucleotide regulatory protein was limiting for beta-adrenergic
signal transduction.(ABSTRACT TRUNCATED AT 250 WORDS)
