D-pro(2)-endomorphin-1 and D-pro(2)-endomorphin-2, respectively, attenuate the antinociception induced by endomorphin-1 and endomorphin-2 given intrathecally in the mouse.
First, the antinociception with the tail-flick test of D-Pro(2)-endomorphin-1 and D-Pro(2)-endomorphin-2 given i.t. was compared with that produced by endomorphin-1 and -2 in male CD-1 mice. High doses of D-Pro(2)-endomorphin-1 (0.2-0.4 pmol) and D-Pro(2)-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) (>90% MPE). Second, coadministration of a low dose of D-Pro(2)-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 of D-Pro(2)-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 that D-Pro(2)-endomorphin-1 and D-Pro(2)-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 mu-opioid receptors.
Hung
Kuei-Chun
KC
Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Wu
Hsiang-En
HE
Mizoguchi
Hirokazu
H
Sakurada
Shinobu
S
Okayama
Toru
T
Fujimura
Tsutomu
T
Murayama
Kimie
K
Sakurada
Tsukasa
T
Fujimoto
James M
JM
Tseng
Leon F
LF
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects
D000701:Analgesics, Opioid; D009842:Oligopeptides; C105293:endomorphin 1; C468133:endomorphin-1, Pro(2)-; C412620:prolyl(2)-endomorphin-2; C105294:endomorphin 2