2P437 Endomorphins analogues containing D-Pro 2 discriminate different μ-opioid receptor mediated antinociception in mice

• Published in: Journal of Pharmacological Sciences 2003, Vol.91 (suppl.1), p.219-219
• Main Authors: Hiroyuki Watanabe, Hiroko Uchiyama, Takafumi Hayashi, Hirokazu Mizoguchi, Akihiko Yonezawa, Tsutomu Fujimura, Kimie Murayama, Tsukasa Sakurada, Shinobu Sakurada
• Format: Article
• Language: Japanese
• ISSN: 1347-8613

The antagonistic actions of D-Pro2-endomorphins (D-Pro2-EMs) on the antinociception induced by endomorphins (EMs) were studied in mice. The antinociception induced by intrathecally (i. t. ) administered endomorphin-1 (EM-1) was significantly attenuated by i, t. co-administration of D-Pro2-endomorphin-1 (D-Pro2-EM-1), but not D-Pro2-endomorphin-2 (D-Pro2-EM-2). On the contrary, the antinociception induced by i, t. administered endomorphin-2 (EM-2) was significantly attenuated by i. t. co-administration of D-Pro2-EM-2, but not D-Pro2-EM-1. In mice pretreated with low dose of naloxonazine, the antinociception induced by i. t, administered EM-2 was significantly antagonized by co-administration of D-Pro2-EM-1, but not D-Pro2-EM-2. Considering with our previous finding that the antinociception induced by i. t. administered EM-1 and EM-2 is mediated by the stimulation of spinal μ2- and μ1-opioid receptor, respectively, the endomorphin analogues containing D-Pr02 may be able to discriminate the antinociceptive response of μ1- and μ2-opioid receptor agonists at the spinal cord level. The action site of EM-2 may be converted from μ1- to μ2-opioid receptor by the pretreatment with low dose of naloxonazine.