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 por tal vein contractions induced by phorbol 12-myristate 13-acetate (PMA) , noradrenaline, endotllelin-1 or KCl, with IC(50)s of 86 nM, 13 mu M, 11 mu M and 9 mu M, respectively. Jatrophone was equipotent to H-7, b ut 100 to 500 fold less potent than staurosporine. Jatrophone, H-7 and staurosporine, also dose-dependently inhibited rhythmic contractions of tile rat portal-mesenteric vein with IC(50)s of 15 mu M, 9 mu M and 75 nM, respectively. Jatrophone, H-7 and staurosporine caused graded relaxations of preparations contracted with endothelin-1 or PMA with I C(50)s of 12 and > 1000 mu M, 8 and 13 mu M and 7 and 12 nM, respectiv ely. All three compounds caused graded inhibition of caffeine-induced contractions in Ca2+-free solution containing EGTA. The similarity bet ween the vasorelaxant actions of jatrophone, staurosporine and H-7 in rat portal vein suggests that jatrophone acts, at least in part, throu gh inhibition of PKC-dependent mechanisms. Moreover, like the PKC inhi bitors, its vasorelaxant action may also involve other mechanisms unre lated to protein kinase C inhibition.