KAPPA-OPIOIDS EXERT A STRONG ANTIPROLIFERATIVE EFFECT ON PC12 RAT PHEOCHROMOCYTOMA CELLS

Pheochromocytomas synthesize several types of opioids and their recept ors. Opioids affect the proliferation rate of normal and tumoral cells . We have previously shown that the PC12 rat pheochromocytoma cells sy nthesize multiple opioids. The aim of the present work was to study th e effect of opioids on the proliferation of these pheochromocytoma cel ls. Thus, the effect of several opioid agonists and antagonists was ex amined on basal and EGF-induced PC12 cell proliferation. The kappa opi oid agonists dynorphin A, U-69593, and U-50488 suppressed basal prolif eration in a dose-dependent manner. The effect of kappa opioids was bl ocked by the general opioid antagonist naloxone and the selective kapp a antagonist nor-binaltorphimine. Furthermore, both opioid antagonists given alone had a strong stimulatory effect, a findings suggesting th at the proliferation of PC12 cells is under tonic inhibition by locall y produced kappa opioids. Finally, the mu-opioid agonist DAGO and the delta and mu agonists DADLE and DSLET were ineffective.