The relaxant action of jatrophone in rat portal vein. A comparison with protein kinase C inhibitors.
Jatrophone, staurosporine and H-7, caused graded inhibition of rat portal vein contractions induced by phorbol 12-myristate 13-acetate (PMA), noradrenaline, endothelin-1 or KCl, with IC50s of 86 nM, 13 microM, 11 microM and 9 microM, respectively. Jatrophone was equipotent to H-7, but 100 to 500 fold less potent than staurosporine. Jatrophone, H-7 and staurosporine, also dose-dependently inhibited rhythmic contractions of the rat portal-mesenteric vein with IC50s of 15 microM, 9 microM and 75 nM, respectively. Jatrophone, H-7 and staurosporine caused graded relaxations of preparations contracted with endothelin-1 or PMA with IC50s of 12 and > 1000 microM, 8 and 13 microM and 7 and 12 nM, respectively. All three compounds caused graded inhibition of caffeine-induced contractions in Ca(2+)-free solution containing EGTA. The similarity between the vasorelaxant actions of jatrophone, staurosporine and H-7 in rat portal vein suggests that jatrophone acts, at least in part, through inhibition of PKC-dependent mechanisms. Moreover, like the PKC inhibitors, its vasorelaxant action may also involve other mechanisms unrelated to protein kinase C inhibition.
Silva
A M
AM
Department of Pharmacology, CCB, UFSC, Brazil.
Brum
R L
RL
Calixto
J B
JB
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D004224:Diterpenes / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011169:Portal Vein; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000470:Alkaloids; D004224:Diterpenes; D016232:Endothelins; D007546:Isoquinolines; D010879:Piperazines; C006386:jatrophone; D002110:Caffeine; D011189:Potassium Chloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine