EFFECTS OF REPEATED ADMINISTRATION OF A K-OPIOID AGONIST ON PHORBOL ESTER BINDING TO MEMBRANE-BOUND PROTEIN-KINASE-C IN RAT-BRAIN

The dissociation constant (K-D) of [H-3]phorbol 12,13-dibutyrate (PDBu ) binding to protein kinase C (PKC) in membranes of rat cortex and mid brain was significantly decreased with no change in the receptor densi ty (B-max) following 7-d treatment with a kappa-opioid agonist, U-50,4 88 (20 mg/kg/d, i.p.), Neither the B-max nor K-D values in pons/medull a were altered by repreated U-50,488 treatment. These results suggest that repeated administration of a kappa-opioid agonist increases the a ffinity for PDBu binding to the membrane-bound PKC in rat cortex and m idbrain, but not in pons/medulla.