Endogenous opioid systems participate in carcinogenic events. To understand further the action of opioids on growth, S20Y neuroblastoma cells in tissue culture were exposed to i) [Met5]-enkephalin, a naturally occurring opioid pentapeptide, at a concentration (10-6 M) that inhibits cell replication by 66% of control levels, ii) [Met5]-enkephalin (10-6 M) and the opioid antagonist naloxone (10-6 M) which blocks opioid agonist action, or iii) naltrexone (10-6 M), a potent antagonist that disrupts endogenous opioid-opioid receptor interaction and increased cell number 76% above control values. The morphology of cells exposed to these agents for 2-4 days were similar to controls (i.e., exposed to sterile water) as determined by scanning and transmission electron microscopy. These results support the hypothesis that endogenous opioid systems act as trophic factors as they regulate growth; their effects on cell growth and survival, however, do not alter the basic ultrastructural morphology of the cells. Moreover, these data strengthen the validity of paradigms and therapeutic regimens that utilize opioid agonists and antagonists to modulate the relationship of endogenous opioid-opioid receptor interactions in neural cancer.
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