OPIOIDS INHIBIT DOPAMINE SECRETION FROM PC12 RAT PHEOCHROMOCYTOMA CELLS IN A NALOXONE-REVERSIBLE MANNER

Opioids inhibit the release of catecholamines in the nervous system. N ormal adrenal chromaffin cells produce delta opioids and they respond to them by suppressing the release of their catecholamines. Chromaffin cell tumors, the pheochromocytomas, produce mainly kappa opioids. The aim of this work was: (a) to test if pheochromocytomas retain the res ponse of normal chromaffin cell catecholamines to delta opioids and to naloxone (a general opioid antagonist), and (b) to test if kappa opio ids exert any specific effect on catecholamine release from these tumo rs. Since we have previously shown that, in common with human pheochro mocytomas, the PC12 rat pheochromocytoma cells express the prodynorphi n gene and secret its kappa opioid products, we used these cells to ex amine the effect of several opioid agonists and of naloxone on basal, nicotine-, and KCl-induced dopamine release. Dopamine is the main PC12 catecholamine. We have found that the specific kappa opioid agonist U -69593 inhibited the release of dopamine in a dose-dependent manner (I C50=0.5 x 10(-8) M). Under basal conditions the mean concentration of dopamine in the culture media was 11.25+/-0.57 ng/mg of total cellular protein (n=13). A 30 min exposure to U-69593 at 10(-6) M suppressed b asal dopamine release to 58+/-2%. (n=7) of controls. A 12 hr pre-incub ation with U-69593 caused the same degree of suppression. The effect o f the synthetic kappa opioid agonist dynorphin A was indistinguishable from that of U-69593. DADLE (a mu and delta synthetic opioid agonist) was significantly less effective in suppressing dopamine release (IC5 0=10(-7) M). The concentration of dopamine following exposure to 10(-6 ) M of DADLE for 30 min was 74+/-5% of the controls (n=4). The mu opio id agonist DAGO was ineffective. The suppressive effect of all opioid agonists was blocked by naloxone suggesting that conventional opioid r eceptors were involved.