PMID: 6168835May 1, 1981Paper

Mechanism of isoprenaline-induced refractoriness of the beta-adrenoceptor--adenylate cyclase system in chick embryo cardiac cells

Journal of Cardiovascular Pharmacology
A BobikG R Campbell

Abstract

We examined the role of beta-adrenoceptors in regulating cardiac cell cyclic adenosine monophosphate (cyclic AMP) in concentrations during beta-receptor activation. Chick embryo cardiac cells in primary tissue culture respond to 50 microM isoprenaline with a rapid, but transient, increase in intracellular cyclic AMP. Continued exposure of these cells to this concentration of isoprenaline results in a rapid time-dependent decrease in maximum beta-receptor responsiveness. In vitro determination of adenylate cyclase and 125I-iodohydroxybenzyl pindolol specific beta-receptor binding sites in 35,000 x g particulate cell fractions and phosphodiesterase activity in cell homogenates suggest that the decrease in the cells' ability to raise intracellular cyclic AMP concentration is mainly due to an initial "uncoupling" of the beta-receptor--adenylate cyclase system. During 16 hr exposure of cells to varying isoprenaline concentrations, the magnitude of the cells' ability to increase intracellular cyclic AMP and the concentration of beta-receptor binding sites were inversely related to the isoprenaline concentration to which they had been previously exposed. On removal of isoprenaline, both beta-receptor response and receptor concentratio...Continue Reading

Citations

Jan 1, 1983·Pharmacology & Therapeutics·N Sperelakis, A J Pappano
Jul 1, 1983·International Journal of Cardiology·J D Marsh
Oct 1, 1993·Journal of the American College of Cardiology·M R Bristow
Jul 22, 1982·The New England Journal of Medicine·M R BristowE B Stinson
Jul 1, 1984·The Journal of Clinical Investigation·M R BristowW Minobe
Jan 1, 1985·Clinical and Experimental Hypertension. Part A, Theory and Practice·A KasserH R Brunner
May 6, 1991·The American Journal of Cardiology·S J VirkM K Davies
Jun 17, 2009·Journal of Cardiovascular Pharmacology·Annick PréfontaineJocelyn Dupuis
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Jan 1, 1983·Acta Medica Scandinavica. Supplementum·A Hedberg
Jul 1, 1983·Muscle & Nerve·G Jasmin, L Proschek

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