Endogenous opioids and the growth regulation of a neural tumor.
Endogenous opioid systems (endogenous opioids and their receptors) are known to participate in the regulation of tumor growth. The present study was conducted to examine whether [Met5]-enkephalin influences the growth of transplanted neuroblastoma, and to explore the role of other opioid peptides in carcinogenesis. A/Jax mice were inoculated with 10(6) S20Y cells and received daily injections of [Met5]-enkephalin. Dosages of 0.5 to 30 mg/kg delayed tumor appearance and prolonged survival of these mice; antitumor effects were blocked by concomitant injections of naloxone. Daily administration (10 mg/kg) of [Leu5]-enkephalin had no effect on neurotumor growth. [D-Ala2, D-Leu5]-enkephalin and ethylketocyclazocine, ligands selective for delta and kappa receptors, respectively, also did not influence neuro-oncogenesis. These results demonstrated the potent growth inhibiting effects of the naturally occurring opioid pentapeptide, [Met5]-enkephalin, and substantiate reports identifying and characterizing an opioid receptor (i.e., zeta) for which [Met5]-enkephalin is the most potent ligand.
Zagon
I S
IS
Department of Anatomy, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
McLaughlin
P
P
D000818:Animals; D000970:Antineoplastic Agents; D004743:Enkephalin, Leucine / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000473:pathology*; D011957:Receptors, Opioid / Q000502:physiology*
D000970:Antineoplastic Agents; D011957:Receptors, Opioid; C062922:zeta receptor; D009270:Naloxone; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine