A Tyr-W-MIF-1 Analog Containing D-Pro2 Acts as a Selective μ2-Opioid Receptor Antagonist in the Mouse
| Autor: | Hiroyuki Watanabe, Takumi Sato, Kimie Murayama, Tsutomu Fujimura, Tsukasa Sakurada, Daisuke Nakayama, Hirokazu Mizoguchi, Kanenori Ito, Chikai Sakurada, Shunsuke Kawamura, Shinobu Sakurada, Chizuko Watanabe |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.drug_class Narcotic Antagonists Receptors Opioid mu Pharmacology Mice chemistry.chemical_compound Opioid receptor otorhinolaryngologic diseases medicine Animals Receptor Naloxone Chemistry 3 4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide (trans)-Isomer Antagonist Enkephalin Ala(2)-MePhe(4)-Gly(5) Receptor antagonist Spinal cord MSH Release-Inhibiting Hormone Naltrexone Analgesics Opioid DAMGO Nociception medicine.anatomical_structure Molecular Medicine Oligopeptides Endomorphin |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 312:1075-1081 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | The antagonistic properties of Tyr-d-Pro-Trp-Gly-NH(2) (d-Pro(2)-Tyr-W-MIF-1), a Tyr-Pro-Trp-Gly-NH(2)(Tyr-W-MIF-1) analog, on the antinociception induced by the mu-opioid receptor agonists Tyr-W-MIF-1, [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), Tyr-Pro-Trp-Phe-NH(2) (endomorphin-1), and Tyr-Pro-Phe-Phe-NH(2) (endomorphin-2) were studied in the mouse paw-withdrawal test. d-Pro(2)-Tyr-W-MIF-1 injected intrathecally (i.t.) had no apparent effect on the thermal nociceptive threshold. d-Pro(2)-Tyr-W-MIF-1 (0.1-0.4 nmol) coadministered i.t. showed a dose-dependent attenuation of the antinociception induced by Tyr-W-MIF-1 without affecting endomorphin- or DAMGO-induced antinociception. However, higher doses of d-Pro(2)-Tyr-W-MIF-1 (0.8-1.2 nmol) significantly attenuated endomorphin-1- or DAMGO-induced antinociception, whereas the antinociception induced by endomorphin-2 was still not affected by d-Pro(2)-Tyr-W-MIF-1. Pretreatment i.t. with various doses of naloxonazine, a mu(1)-opioid receptor antagonist, attenuated the antinociception induced by Tyr-W-MIF-1, endomorphin-1, endomorphin-2, or DAMGO. Judging from the ID(50) values for naloxonazine against the antinociception induced by the mu-opioid receptor agonists, the antinociceptive effect of Tyr-W-MIF-1 is extremely less sensitive to naloxonazine than those of endomorphin-1 or DAMGO. In contrast, endomorphin-2-induced antinociception is extremely sensitive to naloxonazine. The present results clearly suggest that d-Pro(2)-Tyr-W-MIF-1 is the selective antagonist to be identified for the mu(2)-opioid receptor in the mouse spinal cord. d-Pro(2)-Tyr-W-MIF-1 may also discriminate between Tyr-W-MIF-1-induced antinociception and the antinociception induced by endomorphin-1 or DAMGO, all of which show a preference for the mu(2)-opioid receptor in the spinal cord. |
| Databáze: | OpenAIRE |
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