Inhibitory effects of quercetin and staurosporine on phasic contractions in rat vascular smooth muscle.
The aim of this work was to analyze the effects of quercetin and staurosporine on the phasic contractile responses in rat aorta induced by noradrenaline, 5-hydroxytryptamine (5-HT, serotonin) and caffeine in Ca(2+)-free media. Both quercetin and staurosporine inhibited the contractions induced by 10(-5) M noradrenaline, 10(-5) M 5-HT and 20 mM caffeine in Ca(2+)-free solution. Phorbol 12-myristate 13-acetate (5 x 10(-8) M) enhanced this transient contraction elicited by noradrenaline, an effect that was abolished by quercetin (5 x 10(-5) M). The relaxant effects of quercetin on 80 mM KCl induced contractions were similar in normal and low Na+ solution, e.g. when Ca2+ efflux through the Na+/Ca2+ exchanger was inhibited. Furthermore, quercetin or staurosporine had no effect on 45Ca2+ efflux under resting conditions or when stimulated by 10(-5) M noradrenaline. These results suggested that the inhibitory effects of quercetin and staurosporine on phasic contractile responses induced by receptor agonists in Ca(2+)-free media do not seem to be related to changes in cellular Ca2+ regulation but to an inhibitory effect on the regulation of contractile proteins, an effect probably related to the decreased sensitivity of contractile elements to Ca2+ that apparently resulted from the inhibitory effects of quercetin and staurosporine on protein kinases.
Duarte
J
J
Department of Pharmacology, School of Pharmacy, University of Granada, Spain.
Pérez-Vizcaíno
F
F
Zarzuelo
A
A
Jiménez
J
J
Tamargo
J
J
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D012701:Serotonin; D002110:Caffeine; D011189:Potassium Chloride; D011794:Quercetin; D012964:Sodium; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine