Antinociceptive effect of U-50488H, a kappa-opioid agonist, in streptozotocin-induced diabetic mice.
We compared the antinociceptive activity of a kappa-opioid agonist, U-50488H, in streptozotocin-induced diabetic mice with that in non-diabetic mice. Subcutaneously administered U-50488H (3 and 10 mg kg(-1)) showed a more potent antinociceptive effect, as evaluated by the tail-pressure method, in diabetic mice than in non-diabetic mice. Increased antinociceptive activity of U-50488H observed in diabetic mice was also observed in mice given U-50488H intrathecally (3 and 10 microg). However, there were no differences observed between diabetic and non-diabetic mice given U-50488H intracerebroventricularly (3 and 10 microg). Although the antinociceptive effect of U-50488H (3 mg kg(-1), s.c.) in non-diabetic mice was increased by treatment with PD135158 (100 ng, i.c.v.), a cholecystokininB (CCKB) antagonist, the antinociceptive activity of U-50488H which was enhanced in diabetic mice was not influenced by PD135158. Moreover, the increased antinociceptive activity of U-50488H (3 mg kg(-1), s.c.) in diabetic mice diminished when desulfated octapeptide of cholecystokinin (3-100 ng, i.c.v.), a CCKB agonist, was administered. These results suggested that diabetic mice were selectively hyper-responsive to spinal kappa-opioid receptor-mediated antinociception. The function of the analgesia inhibitory system in which cholecystokinin is used as a transmitter might be diminished in diabetic mice.
Suzuki
Y
Y
Kampo and Pharmacognosy Laboratories, Tsumura & Co, Inashiki-gun, Ibaraki, Japan.
Goto
K
K
Shiizaki
K
K
Omiya
Y
Y
Ishige
A
A
Komatsu
Y
Y
Kamei
J
J
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000700:Analgesics; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000662:veterinary; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D010146:Pain / Q000503:physiopathology* / Q000517:prevention & control; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects
D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D000900:Anti-Bacterial Agents; D013311:Streptozocin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D002766:Cholecystokinin