Phosphorylation and adrenergic chronotropism and inotropism in guinea pig cardiac muscles.
A question whether phosphorylation is involved in adrenergic effects on cardiac tissues has long been a matter of dispute. We examined whether phosphorylation is involved in adrenergic chronotropism and inotropism in excised cardiac muscles from guinea pigs. KT5720, a specific inhibitor of A-kinase, abolished the late phase of adrenergic chronotropism. Okadaic acid, an inhibitor of phosphoprotein phosphatases, and IBMX (1-methyl, 3-isobutylxanthine), a phosphodiesterase inhibitor, potentiated the chronotropism. The adrenergic inotropism was influenced neither by KT5720, okadaic acid, nor by IBMX. The specific beta 1 -adrenergic agonist, denopamine, showed actions similar to adrenaline and susceptibility to the inhibitors. Adrenaline of 10 microM showed a chronotropic time course consisting of early and late components. We concluded that only the late component results from phosphorylation, and its early one and the inotropism is entirely independent of phosphorylation.
Gotoh
H
H
Department of Physiology, Iwate Medical University School of Medicine, Japan.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D018663:Adrenergic Agents / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011758:Pyrroles / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism* / Q000502:physiology
D018663:Adrenergic Agents; D000318:Adrenergic beta-Agonists; D002227:Carbazoles; D004988:Ethers, Cyclic; D007211:Indoles; D011758:Pyrroles; D018342:Receptors, Adrenergic, beta-1; D019319:Okadaic Acid; C057416:KT 5720; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine