Pharmacological antagonism of the antinociceptive effects of serotonin in the rat spinal cord.
Pharmacological antagonism of the antinociceptive effects of serotonin in the rat spinal cord.
复制标题
血清素在大鼠脊髓中的抗伤害作用的药理学拮抗作用。
DOI：
10.1016/0014-2999(83)90556-3
复制
发表时间：
1983
影响因子：
5
通讯作者：
Yaksh,TL
中科院分区：
文献类型：
--
作者：
Schmauss,C;Hammond,DL;Ochi,JW;Yaksh,TL
5-羟色胺肌酸酐硫酸盐（5-HT）通过长期植入鞘内导管管理产生了剂量依赖性增加大鼠热板和甩尾反应lasting。为了表征介导该效应的脊髓受体系统的性质，将假定的5-羟色胺拮抗剂与200 μg 5-HT共同给药。在这些实验中，（12-48 nmol），2-溴麦角酰二乙胺（BOL 6-48 nmol）和酮色林（12-73 nmol）呈剂量依赖性地拮抗鞘内注射5-HT的甩尾效应，IC_（50）值为：麦角新碱17.5±2.5 nmol，BOL 26.5±6.5 nmol;酮色林34.5±5.1 nmol螺哌利多（12-44 nmol）和甲麦角林（6-32 nmol）的作用不是剂量依赖性的，尽管在最高剂量下确实发生了可测量的拮抗作用。与甩尾试验结果相反，5-HT拮抗剂均不能减弱5-HT引起的热板潜伏期升高。除螺哌利多外，这些药物均未显示对基线反应的任何影响。在鞘内注射[14 C]5-HT后5、15和45 min处死并解剖大鼠脑和脊髓，发现仅在最长时间间隔时脑中出现显著量的放射性，此时镇痛幅度显著降低，表明这些脊髓药物效应可能是通过对脊髓受体的局部作用产生的。麦角新碱和BOL（具有可测量的5-HT 1结合活性的药物）容易拮抗鞘内注射5-HT的作用，而螺哌利多和酮色林（用于表征5-HT 2结合位点）相对无活性，这表明5-HT 1受体可能在介导5-HT在甩尾中的脊髓效应中起作用，但在热板伤害性感受试验中不起作用。
Serotonin creatinine sulfate (5-HT) administered via chronically implanted intrathecal catheters produced a dose-dependent increase in the rat hot plate and tail flick response latencies. To characterize the nature of the spinal receptor system through which this effect is mediated, putative serotonin antagonists were co-administered with 200 μg of 5-HT. In these experiments, methysergide (12–48 nmol), 2-bromolysergic acid diethylamide (BOL 6–48 nmol) and ketanserin (12–73 nmol) produced a dose-dependent antagonism of the effects of intrathecally administered 5-HT on the tail flick; with the IC50values being: methysergide 17.5±2.5 nmol; BOL 26.5±6.5 nmol; ketanserin 34.5±5.1 nmol The effects of spiroperidol (12–44 nmol) and metergoline (6–32 nmol) were not dose-dependent, although a measurable antagonism did occur at the highest dose. In contrast to the results obtained with the tail flick test, none of the 5-HT antagonists attenuated the elevation of hot plate latency produced by 5-HT. With the exception of spiroperidol, none of these agents showed any effect on the baseline response latencies. Sacrifice and dissection of rat brain and cord at 5, 15 and 45 min after intrathecal [14C]5-HT revealed that significant quantities of radioactivity appeared in brain only at the longest interval, at a time when the magnitude of the analgesia was significantly diminished, indicating that these spinal drug effects were likely produced by a local action on spinal receptors. The ability of methysergide and BOL (agents with measurable 5-HT1binding activity) to readily antagonize the effects of intrathecal 5-HT versus the relative inactivity of spiroperidol and ketanserin, used to characterize the 5-HT2binding site, suggests the likely role of 5-HT1receptors in mediating the spinnal effects of 5-HT in the tail flick, but not the hot plate test of nociception.
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