beta-Adrenergic relaxation and cAMP kinase activation in coronary arterial smooth muscle.
If beta-adrenergic relaxation of smooth muscle is partly mediated by the adenosine 3',5'-cyclic monophosphate (cAMP) system, then beta-stimulation should be correlated to activation of cAMP-dependent protein kinase (cPK). Studies were performed with bovine coronary arterial strips to identify isozymic forms of cPK and to determine if beta-relaxation is correlated to activation of cPK (reflected by elevated ratios of cPK activity without cAMP to cPK activity with cAMP). Both ion exchange chromatography and a new electrophoretic technique revealed two cPK isozymes (types I and II). No change in cPK activity occurred in strips contracted with 30 mM KCl. In contrast, dose- and time-dependent relaxation during beta-stimulation with isoproterenol was highly correlated to parallel increases in cPK activity. Increased cPK activity was inhibited in assays performed with a specific inhibitor of cPK. Both relaxation and activation of cPK were abolished during beta-adrenergic blockade with propranolol. Relaxation by KCl removal or the ionophore R02-2985, unlike beta-mediated relaxation, did not increase cPK activity. These findings show that beta-mediated relaxation of isolated coronary arterial strips specifically activates cPK, and they support the hypothesis that beta-induced relaxation of vascular smooth muscle involves the cAMP system.
D000818:Animals; D002417:Cattle; D002852:Chromatography, Ion Exchange; D000242:Cyclic AMP / Q000494:pharmacology*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*
D007527:Isoenzymes; D011433:Propranolol; D000242:Cyclic AMP; D011494:Protein Kinases; D007545:Isoproterenol