Differential involvement of μ 1-opioid receptors in dermorphin tetrapeptide analogues-induced antinociception

Abstract

The involvement of putative μ 1-opioid receptors in the antinociception induced by the dermorphin tetrapeptide analogues Try- d-Arg-Phe-β-Ala (TAPA) and Tyr- d-Arg-Phe-β-Ala-NH 2 (TAPA-NH 2) was determined in mice, using a tail-pressure test and a formalin test. TAPA and TAPA-NH 2 injected i.c.v. and i.t. produced dose-dependent antinociception in both assays. In the tail-pressure test, the antinociception induced by i.c.v. or i.t. injected TAPA, but not TAPA-NH 2, was significantly attenuated by pretreatment with naloxonazine, a selective antagonist for putative μ 1-opioid receptors. Moreover, naloxonazine also significantly attenuated the antinociception induced by i.c.v. injected TAPA, but not TAPA-NH 2, in the formalin test. In contrast, the antinociception induced by both TAPA and TAPA-NH 2 given i.t. was significantly attenuated by pretreatment with naloxonazine in the formalin test. The present results suggest that TAPA and TAPA-NH 2 should be considered selective agonists for putative μ 1- and μ 2-opioid receptors, respectively. The C-terminal amidation of TAPA-NH 2 may be critical for distinguishing between putative μ 1- and μ 2-opioid receptors.