Epidermal growth factor produces inotropic and chronotropic effects in rat hearts by increasing cyclic AMP accumulation.
Previously we have shown that epidermal growth factor (EGF) stimulates cardiac adenylyl cyclase and increases cAMP accumulation in the rat heart (Nair et al., Biochem. J. 264, 563-571, 1989). Moreover, we have shown that the stimulation of adenylyl cyclase by EGF in heart is mediated via activation of the stimulatory GTP binding regulatory protein Gs alpha (Nair et al., J. Biol. Chem. 265, 21317-21322, 1990). Since cAMP increases the beating rate of hearts, studies were performed to investigate the effects of EGF on mechanical function of the heart and the role of cAMP in mediating the cardiac effects of EGF. In isolated perfused rat hearts EGF (15 nM) decreased perfusion pressure, increased ventricular contractility and heart rate in a manner similar to that observed with the beta-adrenergic receptor agonist isoproterenol (10 nM). In the presence of the adenosine A1 receptor agonist (-)-N6-(R-phenylisopropyl)-adenosine (PIA, 100 nM) which via activation of the inhibitory GTP binding protein Gi inhibits adenylyl cyclase, the effects of EGF on cAMP accumulation in the heart were markedly attenuated. PIA also decreased the ability of EGF and isoproterenol to alter cardiac contractility and beating rate. However, PIA did not attenuate the increase in heart rate and contractility induced by the alpha-adrenergic agonist phenylephrine which does not stimulate cAMP accumulation in the heart. These data suggest that EGF alters cardiac function by increasing cellular cAMP accumulation.
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
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D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate; D008297:Male; D009200:Myocardial Contraction; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D010660:Phenylisopropyladenosine; D004815:Epidermal Growth Factor; D000242:Cyclic AMP