TY - JOUR T1 - <span class="sc">d</span>-Pro<sup>2</sup>-Endomorphin-1 and<span class="sc">d</span>-Pro<sup>2</sup>-Endomorphin-2, Respectively, Attenuate the Antinociception Induced by Endomorphin-1 and Endomorphin-2 Given Intrathecally in the Mouse JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 874 LP - 879 DO - 10.1124/jpet.102.038927 VL - 303 IS - 2 AU - Kuei-chun Hung AU - Hsiang-en Wu AU - Hirokazu Mizoguchi AU - Shinobu Sakurada AU - Toru Okayama AU - Tsutomu Fujimura AU - Kimie Murayama AU - Tsukasa Sakurada AU - James M. Fujimoto AU - Leon F. Tseng Y1 - 2002/11/01 UR - http://jpet.aspetjournals.org/content/303/2/874.abstract N2 - First, the antinociception with the tail-flick test ofd-Pro2-endomorphin-1 andd-Pro2-endomorphin-2 given i.t. was compared with that produced by endomorphin-1 and -2 in male CD-1 mice. High doses of d-Pro2-endomorphin-1 (0.2–0.4 pmol) and d-Pro2-endomorphin-2 (300–800 pmol) given i.t. produced antinociception with low intrinsic activity [about 25% maximum possible effect (MPE)] compared with that of endomorphin-1 (16.4 nmol) and endomorphin-2 (35 nmol) (&gt;90% MPE). Second, coadministration of a low dose ofd-Pro2-endomorphin-1 (0.1 pmol), which given alone did not affect the tail-flick latencies, markedly attenuated the antinociception induced by endomorphin-1 (16.4 nmol) but not by endomorphin-2 (35 nmol). Similarly, coadministration of a low dose ofd-Pro2-endomorphin-2 (200 pmol), which given alone did not affect the tail-flick latencies, significantly attenuated the antinociception induced by endomorphin-2 (35 nmol) and, to a much lesser extent, endomorphin-1 (16.4 nmol). It is concluded thatd-Pro2-endomorphin-1 andd-Pro2-endomorphin-2 at high doses were partial opioid receptor agonists to produce antinociception, and at low doses were opioid receptor antagonists to block selectively the antinociception induced by endomorphin-1 and endomorphin-2, respectively. Furthermore, our results are consistent with the view that the antinociception induced by endomorphin-1 and endomorphin-2 is mediated by the stimulation of different subtypes of μ-opioid receptors. The American Society for Pharmacology and Experimental Therapeutics ER -