REPEATED ADMINISTRATION OF OPIOIDS ALTERS CHARACTERISTICS OF MEMBRANE-BOUND PHORBOL ESTER BINDING IN RAT-BRAIN

Scatchard analysis of saturation binding data indicated that dissociat ion constant (K-D) of [H-3]phorbol 12,13-dibutyrate (PDB) binding to t he membrane-bound protein kinase C of rat cortex and midbrain was sign ificantly decreased following systemic repeated administration of morp hine (mu-opioid receptor agonist) and butorphanol (mu/delta/kappa-mixe d opioid receptor agonist). No change in the receptor density (B-max) of [H-3]PDB binding was found following repeated treatment with morphi ne and butorphanol. On the other hand, neither the B-max nor K-D value s in pons/medulla were altered in these rats. These results suggest th at systemic repeated opioid treatment, such as morphine and butorphano l leads to an increased affinity for phorbol ester binding to the memb rane-bound protein kinase C in rat cortex and midbrain.