ACTIVATION OF PROTEIN-KINASE-C FROM GUINEA-PIG AND RAT VENTRICULAR MUSCLES BY MUSCLIDE-A1 AND ITS (2R,5S)-DIASTEREOMER

The activating effects of musclide-A1, 6-methyl-2,5-heptanediol 5-(hyd rogen sulphate) (la), and its (2R, 5S)- and (2R, SR)-diastereomers on ventricular protein kinase C from guinea-pig and rat were compared wit h other natural compounds derived from musk and non-natural related co mpounds, The (2R, 5S)-diastereomer was most potent among musk-derived compounds and its related non-natural compounds. The activation by la (20 mu M) was produced in the presence of low [Ca2+](0) and phosphatid ylserine like 1,2-dioctanoylglycerol (2 mu M). The activation pattern for peaks eluted by a hydroxyapatite column demonstrated that la activ ates ventricular-specific protein kinase C peak II, suggesting one mec hanism for the beta-adrenergic cardiotonic potentiation by 1a.