CIRCADIAN-TIME RHYTHM OF HEPATIC PROTEIN-KINASE-C OF RATS PRETREATED WITH PHENOBARBITAL

Circadian-time dependent differences of protein kinase C (PKC) activit ies as well as its susceptibility to a phenobarbital caused suppressio n in vivo (40 mg/kg b.i.d. for 3 days) were studied in outbred male Wi star rats weighing 280-360 g. The well-known phenobarbital induction o f cytochrome P-450 and 7-pentylresorufin-O-depentylase (PROD) was asso ciated with inhibition of the hepatic PKC. The activities of the cytos olic and membrane-bound PKC were significantly lower than in the respe ctive controls. Statistically significant circadian-time differences w ere found. The activities of both cytosolic and membrane-bound PKC of control rats were highest in the evening (158% and 131%, respectively, of the morning values). Furthermore, phenobarbital inhibited the enzy me more strongly at 19.00 h than at 07.00 h. Our results suggest that increase of hepatic cytochrome P-450 content as well as induction of P ROD are inversely related with the function of PKC.