In vitro vasorelaxant effects of indolocarbazole and bis-indole protein kinase C inhibitors on rabbit renal arteries.
The effects of 12 compounds, structurally related to the indolocarbazole bacterial metabolite staurosporine, on caffeine-induced contractions in rabbit renal arteries were studied. Eight of these compounds are effective protein kinase C inhibitors, the others are inactive towards the enzyme. The results show a link between the protein kinase C inhibitory activity and the inhibition of vascular smooth muscle contraction. However, a strong inhibition of protein kinase C is required to observe the vasorelaxant effect.
Université Blaise Pascal, Laboratoire de Chimie Organique Biologique, Aubière, France.
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Fabre
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Prudhomme
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000494:pharmacology*
D002227:Carbazoles; D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D002110:Caffeine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C