Role of pertussis toxin-sensitive G-proteins in the analgesic and anesthetic actions of alpha 2-adrenergic agonists in the rat.
Role of pertussis toxin-sensitive G-proteins in the analgesic and anesthetic actions of alpha 2-adrenergic agonists in the rat.
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DOI：
10.1097/00000542-199510000-00022
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发表时间：
1995-10
期刊：
影响因子：
8.8
通讯作者：
Y. Hayashi;B. C. Rabin;T. Guo;M. Maze
中科院分区：
文献类型：
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作者：
Y. Hayashi;B. C. Rabin;T. Guo;M. Maze
背景α2肾上腺素受体与蓝斑中对百日咳毒素(PTX)敏感的G蛋白偶联。在这个部位，对右美托咪定（一种 α2 激动剂）的催眠反应可以通过 PTX 预处理来阻断。对 PTX 敏感的 G 蛋白也可能参与脊髓上或脊髓部位对 α2 激动剂的麻醉和镇痛反应的转导。为了解决这个问题，我们检查了脑室内、鞘内或两者联合给药 PTX 预处理对氟烷 MAC 的影响，以及全身给药 α2 激动剂右美托咪定的麻醉节省和镇痛效果。方法 对大鼠进行脑室内、鞘内以及脑室内/鞘内组合插管，并用 PTX 治疗（脑室内 0 和 2.5 微克；鞘内 0 或 0.5 微克；0 + 0 或 2.5 + 0.5 脑室内 - 鞘内））。 7 天后，测量计算出的 50% 有效剂量的右美托咪定的镇痛效果（甩尾潜伏期）或 MAC 保留效果。为了证实脑室内施用 PTX 是有效的，对脑室周围脑组织中 G 蛋白的核糖基化进行了评估。结果 右美托咪定的镇痛作用可被鞘内注射的 PTX 阻断，但不会被脑室内途径的 PTX 阻断。单独或联合通过鞘内或脑室内途径的 PTX 不会阻断右美托咪定的 MAC 保留作用。然而，脑室内注射 PTX 可以有效地核糖基化 G 蛋白。结论 结合作者之前的报告，这些数据表明右美托咪定的催眠和镇痛反应是通过 PTX 敏感的 G 蛋白偶联 α2 肾上腺素受体转导的，但位于不同的位点（镇痛脊髓；催眠蓝斑）。需要进一步的研究来定位右美托咪定的 MAC 保留作用的精确位点，并确定 PTX 敏感的 G 蛋白是否参与这种反应。
BACKGROUND alpha 2 Adrenoceptors are coupled to G-proteins sensitive to pertussis toxin (PTX) in the locus coeruleus. At this site, the hypnotic response to dexmedetomidine, an alpha 2 agonist, can be blocked by pretreatment with PTX. G-proteins sensitive to PTX may also be involved in the transduction of anesthetic and analgesic responses to alpha 2 agonists at supraspinal or spinal sites. To address this question the effects of pretreatment with PTX administered intracerebroventricularly, intrathecally, or a combination of the two were examined on the MAC for halothane, and the anesthetic-sparing and analgesic effects of a systemically administered alpha 2 agonist, dexmedetomidine. METHODS Rats were cannulated intracerebroventricularly, intrathecally, and with a combination of intracerebroventricular/intrathecal and treated with PTX (0 and 2.5 micrograms intracerebroventricularly; 0 or 0.5 microgram intrathecally; 0 + 0 or 2.5 + 0.5 intracerebroventricular-intrathecal)). After 7 days, either the analgesic (tail-flick latency) or the MAC-sparing effects of a calculated 50% effective dose of dexmedetomidine were measured. To confirm that intracerebroventricularly administered PTX was effective, ribosylation of G-proteins was assessed in periventricular brain tissue. RESULTS The analgesic action of dexmedetomidine was blocked by PTX intrathecally but not by PTX via the intracerebroventricular route. The MAC-sparing action of dexmedetomidine was not blocked by PTX via the intrathecal or intracerebroventricular routes alone or in combination. Yet, intracerebroventricularly administered PTX effectively ribosylated the G-proteins. CONCLUSIONS Taken together with the authors' previous report, these data suggest that the hypnotic and the analgesic responses to dexmedetomidine are transduced via PTX-sensitive G-protein-coupled alpha 2 adrenoceptors but at separate sites (analgesic-spinal; hypnotic-locus coeruleus). Further studies are needed to localize the precise site(s) for the MAC-sparing effect of dexmedetomidine and to establish whether PTX-sensitive G-proteins are involved in this response.