The relaxant action of jatrophone in rat portal vein. A comparison with protein kinase C inhibitors

Abstract

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 IC 50s of 86 nM, 13 μM, 11 μM and 9 μM, 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 IC 50s of 15 μM, 9 μM and 75 nM, respectively. Jatrophone, H-7 and staurosporine caused graded relaxations of preparations contracted with endothelin-1 or PMA with IC 50s of 12 and > 1000 μM, 8 and 13 μM and 7 and 12 nM, respectively. All three compounds caused graded inhibition of caffeine-induced contractions in Ca -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.