title: Spinal involvement of both dynorphin A and Met-enkephalin in the antinociception induced by intracerebroventricularly administered bremazocine but not morphine in the mouse.
abstract: Previous reports show the tail-flick inhibition induced by bremazocine given i.c.v. is mediated by supraspinal stimulation of both epsilon and kappa opioid receptors and the spinal activation of descending serotonergic and opioid systems. The present studies questioned what endogenous opioid peptides in the spinal cord were involved in i.c.v. bremazocine-induced antinociception in male ICR mice. beta-Endorphin, trans(+-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]- benzene-acetamide methane sulfonate (U50,488H) and morphine were used as reference compounds for epsilon, kappa and mu opioid receptor activity, respectively. Intrathecal pretreatment with antibody to Met-enkephalin dose-dependently attenuated the antinociception induced by i.c.v. bremazocine or beta-endorphin but not morphine or U50,488H; whereas intrathecal (i.t.) pretreatment with antibody to dynorphin A (1-13) dose-dependently blocked the antinociception induced by i.c.v. bremazocine or U50,488H but not beta-endorphin or morphine. Intrathecal Leu-enkephalin and beta-endorphin antibodies did not block i.c.v. bremazocine, beta-endorphin or morphine antinociception. Intrathecal Met-enkephalin or dynorphin A (1-17) increased the tail-flick latency at 1 to 2 min. Met-enkephalin given i.t. blocked the antinociception induced by i.c.v. DPDPE, bremazocine and beta-endorphin but not morphine or U50,488H whereas i.t. dynorphin A (1-17) pretreatment blocked the inhibition induced by i.c.v. U50,488H and bremazocine but not DPDPE, beta-endorphin or morphine. Bremazocine given i.c.v. did not exhibit antianalgesic activity in our studies. The dynorphin released by i.c.v. bremazocine for antinociception appears to be different from the dynorphin released by morphine for antianalgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
authors.forename: L F
authors.initials: LF
authors.lastname: Tseng
authors.forename: K A
authors.initials: KA
authors.lastname: Collins
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000818:Animals; D001575:Benzomorphans; D004347:Drug Interactions; D004399:Dynorphins / Q000378:metabolism* / Q000502:physiology; D004743:Enkephalin, Leucine / Q000502:physiology; D004744:Enkephalin, Methionine / Q000378:metabolism* / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D011759:Pyrrolidines; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors; D001615:beta-Endorphin / Q000502:physiology
chemical_list: D001575:Benzomorphans; D011759:Pyrrolidines; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D009020:Morphine; C027248:bremazocine