Effects of repeated administration of a kappa-opioid agonist on phorbol ester binding to membrane-bound protein kinase C in rat brain.

The dissociation constant (KD) of [3H]phorbol 12,13-dibutyrate (PDBu) binding to protein kinase C (PKC) in membranes of rat cortex and midbrain was significantly decreased with no change in the receptor density (Bmax) following 7-d treatment with a kappa-opioid agonist, U-50,488 (20 mg/kg/d, i.p.). Neither the Bmax nor KD values in pons/medulla were altered by repeated U-50,488 treatment. These results suggest that repeated administration of a kappa-opioid agonist increases the affinity for PDBu binding to the membrane-bound PKC in rat cortex and midbrain, but not in pons/medulla.