Involvement of spinal μ1-opioid receptors on the Tyr-d-Arg-Phe-sarcosine-induced antinociception

The involvement of spinal μ-opioid receptor subtypes on the antinociception induced by i.t.-administered Tyr-d-Arg-Phe-sarcosine (TAPS), a N-terminal tetrapeptide analog of dermorphin, was determined in mice tail-flick test. Intrathecal administration of TAPS produced the marked inhibition of the tail-flick response in a dose-dependent manner. The antinociception induced by TAPS was completely eliminated by i.t.-co-administration of Tyr-d-Pro-Phe-Phe-NH2 (d-Pro2-endomorphin-2), the μ1-opioid receptor antagonist, whereas i.t. co-treatment with Tyr-d-Pro-Trp-Phe-NH2 (d-Pro2-endomorphin-1) or Tyr-d-Pro-Trp-Gly-NH2 (d-Pro2-Tyr-W-MIF-1), the μ2-opioid receptor antagonists, did not affect the TAPS-induced antinociception. In contrast, the antinociception induced by i.t.-administered [d-Ala2,N-MePhe4,Gly-ol5]enkephalin was significantly attenuated by i.t.-co-administration of d-Pro2-endomorphin-1 or d-Pro2-Tyr-W-MIF-1, but not d-Pro2-endomorphin-2. These results suggest that TAPS may stimulate spinal μ1-opioid receptors to produce the antinociception.