Opioids transiently prevent activation of apoptotic mechanisms following short periods of serum withdrawal

Opioids exert a proapoptotic effect on several normal and tumoral cells. Th e aim of the present article was to examine the effect of opioids on the PC 12 rat pheochromocytoma cell line, a model for the study of chromaffin cell apoptosis. These cells produce delta- and K-opioid agonists and their rece ptors. Our results were as follows: The kappa- and delta(2)-opioid receptor agonists had a rapid but transient effect on apoptosis at 3 h, whereas mu opioids did not. The effect of opioids was reversible by the opioid antagon ists naloxone and nor-binaltorphimine. The effect of opioids was protective , suppressing serum deprivation-induced apoptosis to similar to 50% of cont rols. The protective effect of opioids on PC12 apoptosis was measurable onl y under serum deprivation. The effect of opioids was remarkably reproducibl e and highly constant in timing, which did not appear to depend on the dura tion of the preceding serum deprivation. Finally, opioids prevented the ele vation of the Bcl-2 and Bak proteins following serum deprivation to the lev els attained by serum supplementation. Our combined data suggest that opioi ds protect PC12 cells from entering a state of induced apoptosis following serum deprivation.