Increased release of immunoreactive dynorphin A1-17 from the spinal cord after intrathecal treatment with endomorphin-2 in anesthetized rats.
We previously demonstrated pretreatment with antiserum against dynorphin A1-17 attenuates endomorphin-2-induced analgesia and antianalgesia, suggesting that these endomorphin-2 effects are mediated by the release of dynorphin A1-17. Lumbar-cisternal spinal perfusion was used to measure the release of immunoreactive dynorphin A1-17 into spinal perfusates from urethane-anesthetized rats following endomorphin-2 or endomorphin-1 treatment within the perfusion solution. Treatment with endomorphin-2 (5-50 nmol) for 3 min caused a dose-dependent increase of immunoreactive dynorphin A1-17 in spinal perfusates, with a maximal increase detected between 24 and 48 min after endomorphin-2 treatment, while levels returned to baseline within 60 min. Endomorphin-2-induced release of immunoreactive dynorphin A1-17 was attenuated by pretreatment with mu-opioid receptor antagonist naloxone or 3-methoxynaltrexone. Endomorphin-1 induced a slight increase in immunoreactive dynorphin1-17 as well, but only at the highest dose used (50 nmol). Our results suggest that endomorphin-2 stimulated a specific subtype of mu-opioid receptor to induce the release of immunoreactive dynorphin A1-17 in spinal cords of rats.
Leitermann
Randy J
RJ
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Terashvili
Maia
M
Mizoguchi
Hirokazu
H
Wu
Hsiang-En
HE
Chen
Franklin
F
Clithero
Andrew
A
Tseng
Leon F
LF
D000758:Anesthesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007278:Injections, Spinal; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D009270:Naloxone; C105294:endomorphin 2; D004399:Dynorphins