E. Dermitzaki et al., Opioids transiently prevent activation of apoptotic mechanisms following short periods of serum withdrawal, J NEUROCHEM, 74(3), 2000, pp. 960-969
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.