[Met]enkephalin in the spinal cord is involved in the antinociception induced by intracerebroventricularly-administered etorphine in the mouse.
We have recently reported that the antinociception induced by etorphine given i.c.v. is mediated in part by the stimulation of both mu- and epsilon-opioid receptors and the activation of both monoaminergic and opioidergic descending pain control systems. [Xu J. Y. et al. (1992) J. Pharmac. exp. Ther. 263, 246-252]. Since the opioid epsilon-receptor-mediated antinociception induced by beta-endorphin is mediated by the release of [Met]enkephalin and subsequent stimulation of delta-opioid receptors in the spinal cord, the present studies were designed to determine if beta-endorphin-like action is also involved in etorphine-induced antinociception. The tail-flick test was used to assess the antinociceptive response performed in male ICR mice. Etorphine at doses from 5 to 20 ng given i.c.v. produced a dose-dependent inhibition of the tail-flick response. The inhibition of the tail-flick response induced by etorphine given i.c.v. was antagonized by intrathecal pretreatment for 60 min with antiserum against [Met]enkephalin (10 microg), but not with antiserum against [Leu]enkephalin (10 microg) or dynorphin A (1-13) (10 microg). Desensitization of delta-opioid receptors in the spinal cord by intrathecal pretreatment with [Met]enkephalin (5 microg) for 60 min attenuated i.c.v. administered etorphine-induced tail-flick inhibition. However, intrathecal pretreatment with [Leu]enkephalin (5 microg) or dynorphin A (1-17) (0.1 microg) for 60 min did not attenuate i.c.v. administered etorphine-induced tail-flick inhibition. The results indicate that antinociception induced by etorphine given i.c.v. is mediated in part by the stimulation of the epsilon-opioid receptor at the supraspinal sites and by the release of [Met]enkephalin, which subsequently stimulates delta-opioid receptors in the spinal cord.
Xu
J Y
JY
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Tseng
L F
LF
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D019138:Antibodies, Blocking; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000276:immunology / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005048:Etorphine / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017480:Receptors, sigma / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D000701:Analgesics, Opioid; D019138:Antibodies, Blocking; D017465:Receptors, Opioid, delta; D017480:Receptors, sigma; D005048:Etorphine; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D004399:Dynorphins