Involvement of endogenous opioid peptides in the antinociception induced by the novel dermorphin tetrapeptide analog amidino-TAPA
| Autor: | Akihiko Yonezawa, Hirokazu Mizoguchi, Chizuko Watanabe, Kaori Moriyama, Shinobu Sakurada, Tsukasa Sakurada, Hiroyuki Watanabe, Bunsei Sato, Keiko Ohwada |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Enkephalin medicine.drug_class Dynorphin Pharmacology chemistry.chemical_compound Mice Opioid receptor Naltrindole GTP-Binding Proteins Internal medicine medicine Animals Opioid peptide Injections Spinal Mice Knockout Analgesics Chemistry Dynorphin B Dynorphin A Dermorphin Enkephalin Ala(2)-MePhe(4)-Gly(5) Mice Inbred C57BL Endocrinology Opioid Peptides Guanosine 5'-O-(3-Thiotriphosphate) Enkephalin D-Penicillamine (2 5) Oligopeptides medicine.drug |
| Zdroj: | European journal of pharmacology. 560(2-3) |
| ISSN: | 0014-2999 |
| Popis: | The antinociceptive effect of i.t. administered N(alpha)-amidino-Tyr-d-Arg-Phe-beta-Ala (amidino-TAPA), an N-terminal tetrapeptide analog of dermorphin, was characterized in ddY mice. In the opioid receptor ligand-binding assays using mouse brain membranes, amidino-TAPA showed a very high affinity for mu-opioid receptors, a low affinity to delta-opioid receptors and no affinity for kappa-opioid receptors. In the mouse tail-flick test, i.t. treatment with amidino-TAPA produced a potent antinociception. The antinociception induced by amidino-TAPA was significantly attenuated by i.t. pretreatment with the mu-opioid receptor antagonist beta-funaltrexamine, the kappa-opioid receptor antagonist nor-binaltorphimine and the delta-opioid receptor antagonist naltrindole. Moreover, the antinociception induced by amidino-TAPA was significantly attenuated by i.t. pretreatment with antisera against the endogenous kappa-opioid peptides dynorphin A, dynorphin B and alpha-neo-endorphin; and the endogenous delta-opioid peptide [Leu(5)]enkephalin. In mice lacking prodynorphin, the precursor of the endogenous kappa-opioid peptides, the antinociceptive effect of amidino-TAPA was significantly attenuated compared to that in wild-type C57BL/6J mice. However, there was no difference in G-protein activation by amidino-TAPA in the spinal cord membranes from prodynorphin knockout mice and C57BL/6J mice. The present results suggest that the spinal antinociception induced by the mu-opioid receptor selective peptide amidino-TAPA is mediated in part by the release of endogenous opioid peptides in the spinal cord, which is caused by the direct stimulation of mu-opioid receptors. |
| Databáze: | OpenAIRE |
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