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 staur osporine on the phasic contractile responses in rat aorta induced by n oradrenaline, 5-hydroxytryptamine (5-HT, serotonin) and caffeine in Ca 2+-free media. Both quercetin and staurosporine inhibited the contract ions induced by 10(-5) M noradrenaline, 10(-5) M 5-HT and 20 mM caffei ne in Ca2+-free solution. Phorbol 12-myristate 13-acetate (5 x 10(-8) M) enhanced this transient contraction elicited by noradrenaline, an e ffect that was abolished by quercetin (5 X 10(-5) M). The relaxant eff ects of quercetin on 80 mM KCl induced contractions were similar in no rmal and low Na+ solution, e.g. when Ca2+ efflux through the Na+/Ca2exchanger was inhibited. Furthermore, quercetin or staurosporine had n o effect on Ca-45(2+) efflux under resting conditions or when stimulat ed by 10(-5) M noradrenaline. These results suggested that the inhibit ory effects of quercetin and staurosporine on phasic contractile respo nses induced by receptor agonists in Ca2+-free media do not seem to be related to changes in cellular Ca2+ regulation but to an inhibitory e ffect on the regulation of contractile proteins, an effect probably re lated to the decreased sensitivity of contractile elements to Ca2+ tha t apparently resulted froth the inhibitory effects of quercetin and st aurosporine on protein kinases.