Possible involvement of protein kinase C in the modulation of inotropic and chronotropic effects induced by ouabain in rat right atrial muscles.
Modulations of the inotropic and chronotropic effects of ouabain and protein kinase C (PKC) stimulation with phorbol esters in rat right atria were examined. Cumulative administration of ouabain (3-30 microM) caused a positive inotropic effect in a concentration-dependent manner, but did not produce a chronotropic effect. A single administration of ouabain (30 microM) also had similar effects: + 74.4 +/- 8.4% (n = 23, P < 0.01) in the contractile force and -0.7 +/- 1.3% (n = 23, P > 0.05) in the sinus rate. Addition of phorbol esters reinforced the ouabain-evoked positive inotropic effect: 26.5 +/- 8.9% (n = 6, P < 0.05) with 100 microM 4-beta-phorbol-12,13-dibutyrate (PDB), and 6.4 +/- 3.3% (n = 6, P > 0.05) with 100 microM 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Simultaneously, the mixture of ouabain and phorbol ester raised the resting tension. Phorbol esters alone caused a positive inotropic effect (by about 21-27%). Non-PKC activating phorbol ester, 4-alpha-phorbol-12,13-didecanoate (PDD, 100 microM), did not have any effect. Pretreatment with the PKC inhibitor (staurosporine 100 microM) significantly decreased the ouabain-induced positive inotropic effect and caused a negative chronotropic effect, but H-7 (1-(5-isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride) (5 microM) had no effect. These results suggest that PKC stimulation may be involved in the ouabain-evoked responses in the right atria of rat as seen by increased cellular Ca2+ concentration (and Ca(2+)-sensitivity); thus the positive inotropic effect may not be due only to modulation of Na+/K+ pump activity.
Satoh
H
H
Department of Pharmacology, Nara Medical University, Japan. hysat@nmu-gw.cc.naramed-u.ac.jp
Narushima
I
I
Nakashima
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000201:enzymology; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010703:Phorbol Esters; D010042:Ouabain; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine