ROLE OF CENTRAL ATP-SENSITIVE POTASSIUM CHANNELS IN THE ANALGESIC EFFECT AND SPINAL NORADRENALINE TURNOVER-ENHANCING EFFECT OF INTRACEREBROVENTRICULARLY INJECTED MORPHINE IN MICE
ROLE OF CENTRAL ATP-SENSITIVE POTASSIUM CHANNELS IN THE ANALGESIC EFFECT AND SPINAL NORADRENALINE TURNOVER-ENHANCING EFFECT OF INTRACEREBROVENTRICULARLY INJECTED MORPHINE IN MICE
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DOI：
10.1016/0006-8993(92)91549-t
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发表时间：
1992-11-20
期刊：
影响因子：
2.9
通讯作者：
TAKAHATA, N
中科院分区：
文献类型：
--
作者：
NARITA, M;SUZUKI, T;TAKAHATA, N
格列本脲是最有效的磺脲类降糖药之一，它可以阻断三磷酸腺苷敏感钾（K(ATP)）通道。在本研究中，我们发现吗啡、u -50,488（一种选择性卡帕激动剂）和巴氯芬（一种选择性GABA(B)激动剂）在10(-4)M浓度的培养培养基中对[环己基-2,3-H-3(N)]格列本脲（[H-3]格列本脲）与分离的小鼠脑微粒体的特异性结合没有明显影响。小鼠脑室内注射吗啡而非u -50,488 - 8h诱导的镇痛活性可通过格列本脲或-富纳曲胺（β - fna，一种选择性拮抗剂）预处理而拮抗。此外，吗啡对脊髓去甲肾上腺素（NA）转换的增加作用被β - fna或格列本脲预处理大大拮抗。从这些结果中，我们证明了K（ATP）通道作为mu激动剂而非kappa激动剂诱导的小鼠椎上镇痛的间接调节剂发挥了重要作用，并且K（ATP）通道的阻断似乎抑制了吗啡诱导的降去甲肾上腺素能系统的激活。
Glibenclamide is one of the most potent sulfonylurea-derived antidiabetic drugs which block the adenosine triphosphate-sensitive potassium (K(ATP)) channels. In the present study, we found that none of morphine, U-50,488H (a selective kappa agonist) and baclofen (a selective GABA(B) agonist) added to the incubation medium at concentrations up to 10(-4) M had appreciable effect on the specific binding of [cyclohexyl-2,3-H-3(N)]glibenclamide ([H-3]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 K(ATP) 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 K(ATP) channels.