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To test our hypothesis that the abnormally low efficacy of mu-opioid agonists in diabetic mice may be due to functional changes in ATP-sensitive potassium channels, we evaluated the effects of cromakalim on the tail-flick latencies in diabetic and non-diabetic mice. Anti nociceptive effects of morphine (10 micrograms, ICV) in diabetic mice were significantly less than that in non-diabetic mice. Morphine-induced antinociception in non-diabetic mice was antagonized by pretreatment with glibenclamide (30 micrograms, ICV), an ATP-sensitive potassium channel blocker. Cromakalim (0.3 and 1 micrograms, ICV) produced significant, dose-dependent antinociception in non-diabetic mice, which was significantly reduced by pretreatment with glibenclamide. However, cromakalim did not markedly affect the tail-flick latencies in diabetic mice, even at higher doses (3 micrograms, ICV). On the other hand, [D-Pen2,5]enkephaline (DPDPE, 5 micrograms, ICV), a selective delta-opioid receptor agonist, produced significant antinociception in both diabetic and non-diabetic mice. Since pretreatment with glibenclamide significantly reduced the antinociceptive effect of DPDPE in non-diabetic mice but not in diabetic mice, delta-opioid receptor-mediated antinociception in diabetic mice may be independent of potassium channels. These results suggest that dysfunction of ATP-sensitive potassium channels may contribute to the demonstrated poor antinociceptive response of diabetic mice to mu-opioid agonists.
J Kamei, and
N Kawashima, and
M Narita, and
T Suzuki, and
M Misawa, and
Y Kasuya
October 1997,
Nihon rinsho. Japanese journal of clinical medicine,
J Kamei, and
N Kawashima, and
M Narita, and
T Suzuki, and
M Misawa, and
Y Kasuya
September 1999,
Acta anaesthesiologica Sinica,
J Kamei, and
N Kawashima, and
M Narita, and
T Suzuki, and
M Misawa, and
Y Kasuya
May 1995,
Nihon Naibunpi Gakkai zasshi,
J Kamei, and
N Kawashima, and
M Narita, and
T Suzuki, and
M Misawa, and
Y Kasuya
January 1990,
Ion channels,
J Kamei, and
N Kawashima, and
M Narita, and
T Suzuki, and
M Misawa, and
Y Kasuya
June 1994,
Cardiovascular research,
J Kamei, and
N Kawashima, and
M Narita, and
T Suzuki, and
M Misawa, and
Y Kasuya
July 2015,
The Journal of endocrinology,
J Kamei, and
N Kawashima, and
M Narita, and
T Suzuki, and
M Misawa, and
Y Kasuya
January 2017,
Cell,
J Kamei, and
N Kawashima, and
M Narita, and
T Suzuki, and
M Misawa, and
Y Kasuya
July 2015,
Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
J Kamei, and
N Kawashima, and
M Narita, and
T Suzuki, and
M Misawa, and
Y Kasuya
November 1993,
Journal of medicinal chemistry,
J Kamei, and
N Kawashima, and
M Narita, and
T Suzuki, and
M Misawa, and
Y Kasuya
August 2019,
Nature,
