Bestatin potentiates the antinociception but not the motor dysfunction induced by intracerebrally administered dynorphin-B in mice.
The intracerebrally administered dynorphin-B produced not only an antinociceptive response but a motor dysfunction such as "barrel-rolling", circling, jumping or ataxia in mice. These two effects were observed in a same dose range. Both responses were also produced by a nonopioid fragment, des-Tyr-dynorphin-B. Bestatin, an aminopeptidase inhibitor, markedly potentiated the antinociceptive response induced by dynorphin-B but not the motor dysfunction. Bestatin did not affect the responses produced by des-Tyr-dynorphin-B. In the presence of bestatin, low doses of dynorphin-B produced an antinociceptive response without the motor dysfunction. Naloxone antagonized the potentiated antinocicpetion but had no effect on the motor dysfunction. These results suggest that dynorphin-B produced an analgesia through opioid receptors and that this peptide also induced a motor dysfunction through a nonopioid receptor.
Nakazawa
T
T
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Ikeda
M
M
Kaneko
T
T
Yamatsu
K
K
Kitagawa
K
K
Kiso
Y
Y
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000698:Analgesia; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004399:Dynorphins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004723:Endorphins / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000502:physiology
D004723:Endorphins; D011957:Receptors, Opioid; D009270:Naloxone; D004399:Dynorphins; C036200:rimorphin; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex