Opioids Transiently Prevent Activation of Apoptotic Mechanisms Following Short Periods of Serum Withdrawal

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Abstract
Opioids exert a proapoptotic effect on several normal and tumoral cells. The aim of the present article was to examine the effect of opioids on the PC12 rat pheochromocytoma cell line, a model for the study of chromaffin cell apoptosis. These cells produce δ‐ and κ‐opioid agonists and their receptors. Our results were as follows: The κ‐ and δ2‐opioid receptor agonists had a rapid but transient effect on apoptosis at 3 h, whereas μ opioids did not. The effect of opioids was reversible by the opioid antagonists naloxone and nor‐binaltorphimine. The effect of opioids was protective, suppressing serum deprivation‐induced apoptosis to ∼50% of controls. The protective effect of opioids on PC12 apoptosis was measurable only under serum deprivation. The effect of opioids was remarkably reproducible and highly constant in timing, which did not appear to depend on the duration of the preceding serum deprivation. Finally, opioids prevented the elevation of the Bcl‐2 and Bak proteins following serum deprivation to the levels attained by serum supplementation. Our combined data suggest that opioids protect PC12 cells from entering a state of induced apoptosis following serum deprivation.