| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2006153 | Peptides | 2013 | 6 Pages |
•TAPA is μ-opioid receptor agonist does not have the affinity for κ-opioid receptors.•Spinal antinociception of TAPA is selectively mediated by spinal μ1-opioid receptors.•Spinal antinociception of TAPA is also mediated by spinal κ-opioid receptors.•Spinal antinociception of TAPA is mediated through the spinal release of α-neo-endorphin.•The multiple μ1-opioid receptors are involved in the spinal antinociception of TAPA.
The antinociceptive effect of i.t.-administered Tyr-d-Arg-Phe-β-Ala (TAPA), an N-terminal tetrapeptide analog of dermorphin, was characterized in ddY mice. In the mouse tail-flick test, TAPA administered i.t. produced a potent antinociception. The antinociception induced by TAPA was significantly attenuated by i.t. pretreatment with the κ-opioid receptor antagonist nor-binaltorphimine, as well as by the μ-opioid receptor antagonist β-funaltrexamine and the μ1-opioid receptor antagonist naloxonazine. TAPA-induced antinociception was also significantly suppressed by co-administration of the μ1-opioid receptor antagonist Tyr-d-Pro-Phe-Phe-NH2 (d-Pro2-endomorphin-2) but not by co-administration of the μ2-opioid receptor antagonists Tyr-d-Pro-Trp-Phe-NH2 (d-Pro2-endomorphin-1) and Tyr-d-Pro-Trp-Gly-NH2 (d-Pro2-Tyr-W-MIF-1). In CXBK mice whose μ1-opioid receptors were naturally reduced, the antinociceptive effect of TAPA was markedly suppressed compared to the parental strain C57BL/6ByJ mice. Moreover, the antinociception induced by TAPA was significantly attenuated by i.t. pretreatment with antiserum against the endogenous κ-opioid peptide α-neo-endorphin but not antisera against other endogenous opioid peptides. In prodynorphin-deficient mice, the antinociceptive effect of TAPA was significantly reduced compared to wild-type mice. These results suggest that the spinal antinociception induced by TAPA is mediated in part through the release of α-neo-endorphin in the spinal cord via activation of spinal μ1-opioid receptors.
