Role of central ATP-sensitive potassium channels in the analgesic effect and spinal noradrenaline turnover-enhancing effect of intracerebroventricularly injected morphine in mice.
Glibenclamide is one of the most potent sulfonylurea-derived antidiabetic drugs which block the adenosine triphosphate-sensitive potassium (KATP) channels. In the present study, we found that none of morphine, U-50,488H (a selective kappa agonist) and baclofen (a selective GABAB agonist) added to the incubation medium at concentrations up to 10(-4) M had appreciable effect on the specific binding of [cyclohexyl-2,3-3H(N)]glibenclamide ([3H]glibenclamide) to the isolated mouse brain microsomes. The analgesic activity induced by intracerebroventricular injection (i.c.v.) of morphine but not U-50,488H was antagonized by pretreatment with either i.c.v. glibenclamide or beta-funaltrexamine (beta-FNA; a selective mu antagonist) in mice. Furthermore, the increasing effect of i.c.v. morphine on the spinal noradrenaline (NA) turnover was greatly antagonized by i.c.v. pretreatment with either beta-FNA or glibenclamide. From these results, we demonstrated that KATP channels play an important role as indirect modulators of the supraspinal analgesia induced by mu agonist but not kappa agonist in mice, and the activation of descending noradrenergic system induced by i.c.v. morphine appears to be suppressed by the blockade of KATP channels.
Narita
M
M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Suzuki
T
T
Misawa
M
M
Nagase
H
H
Nabeshima
A
A
Ashizawa
T
T
Ozawa
H
H
Saito
T
T
Takahata
N
N
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000698:Analgesia; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D005905:Glyburide / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism*
D015221:Potassium Channels; D011759:Pyrrolidines; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D000255:Adenosine Triphosphate; D001418:Baclofen; D005905:Glyburide; D009638:Norepinephrine