title: Adenosine 3',5'-cyclic monophosphate in perfused rat hearts exposed to isoprenaline and dopamine.
abstract: Isoprenaline and dopamine increased cyclic AMP (cAMP) content and contractile activity of isolated perfused rat hearts. The changes of cAMP levels depended on the mode of drug administration. Isoprenaline (4 x 10(-10) mol) administered to the perfused heart as a relatively concentrated bolus, caused a substantial, rapid and transient increase of cAMP. Isoprenaline (2 x 10(-10) mol and 4 x 10(-10) mol) and dopamine (10(-7) mol) diluted in 40 ml of perfusate which was continuously recirculated through the heart, caused a gradual increase of cAMP content which approached an apparent steady state. cAMP accumulation occurred at isoprenaline concentrations above 10(-9) M and at dopamine concentrations above 10(-6) M. Both agents also increased cAMP labelling from 14C-adenine in the perfusate, probably indicating increased cAMP synthesis. Isoprenaline at 2 x 10(-8) M and 10(-7) M increased labelling more than content of cAMP. Isoprenaline and dopamine also increased phosphorylase a activity. An association between increased cAMP contents and increased contractile activity was revealed by both the time-response and the dose-response curves of hearts exposed to isoprenaline and dopamine. Since both agents stimulate adrenergic beta-receptors in cardiac muscle, the results are concordant with the hypothesis that cAMP is involved as a mediator of the inotropic response to adrenergic beta-stimulation.
mesh_terms: D000225:Adenine / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D013268:Stimulation, Chemical
chemical_list: D000242:Cyclic AMP; D006005:Phosphorylases; D000225:Adenine; D007545:Isoproterenol; D004298:Dopamine