Yuanhuacin A is a selective antagonist of phorbol ester receptor in protein kinase C.

Protein kinase C with a molecular weight of 82 kD has been purified to electrophoresis homogeneous from rat brain through a series of chromatography columns including DE-52, Sepharose G-200 and phenyl-Sepharose. The enzyme possessed autophosphorylation activity. Yuanhuacin A inhibited the 3H-phorbol-12, 13-dibutyrate (3H-PdBu) binding of PKC with an IC50 value of 1.48 +/- 0.28 x 10(-8) mol/L when the concentration of 3H-PdBu was 1.5 x 10(-9) mol/L (Ki = 1.2 x 10(-8) mol/L). Yuanhuacin A inhibited the PdBu-stimulated PKC activity in the catalysis of the phosphorylation of Histone III-S with an IC50 of 2.82 +/- 0.37 x 10(-9) mol/L (PdBu = 10(-6) mol/L), while it had no effect on the basal and Ca(2+)-stimulated PKC activity in the same assay system. This result suggests that Yuanhuacin A is a selective antagonist of the phorbol ester receptor in protein kinase C.