Beta-adrenergic receptor regulation during hypoxia in intact cultured heart cells.
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)
Marsh
J D
JD
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Sweeney
K A
KA
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000096:biosynthesis; D006321:Heart / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011412:Propanolamines / Q000378:metabolism; D011433:Propranolol / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D011433:Propranolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C033394:CGP 12177