INTRATHECAL BRADYKININ ACTS PRESYNAPTICALLY ON SPINAL NORADRENERGIC TERMINALS TO PRODUCE ANTINOCICEPTION IN THE RAT
INTRATHECAL BRADYKININ ACTS PRESYNAPTICALLY ON SPINAL NORADRENERGIC TERMINALS TO PRODUCE ANTINOCICEPTION IN THE RAT
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DOI：
10.1016/0014-2999(89)90158-1
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发表时间：
1989-01-17
影响因子：
5
通讯作者：
COUTURE, R
中科院分区：
文献类型：
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作者：
LANEUVILLE, O;READER, TA;COUTURE, R
在清醒的束缚大鼠中，鞘内（i. th.）给药8.1 pmol-8.1 nmol缓激肽（BK）和激肽（KD）以剂量依赖性方式增加对有害辐射热刺激的反应时间（RT）。片段BK-（1-8）和BK-（1-7）仅在高于10 nmol的剂量下才有活性，并且观察到以下效力等级顺序：BK > KD. mchgt。BK-（1-8）> BK（1-7）。甩尾潜伏期在给药后1（BK）或6（KD）min时增加最大，RT在给药后15 min内恢复至基础水平。BK（81 pmol）的作用不受先前i.普萘洛尔和纳洛酮可显著增强上述作用（P < 0.05）。而对BK的反应则明显被阻断（P < 0.05）。相比之下，对BK的反应被酚妥拉明、咪唑克生和育亨宾以及用20 μ g（i.th.）一周前。后者预处理降低了i. th的抗伤害效应。酪胺（7 μ mol）增强去甲肾上腺素（NA）（0.6 nmol）的镇痛作用（P < 0.01），同时保持神经激肽B（8 nmol）的镇痛作用和P物质（6.5 nmol）的痛觉过敏作用。生化分析显示，6-OHDA治疗使腰脊髓中的NA含量减少了60%，而不影响血清素、多巴胺、肾上腺素或其主要代谢物的水平。颈髓（44%）和胸髓（55%）的NA含量也显著降低。用6-OHDA预处理较长的生存期（2周）导致腰髓NA进一步降低（88%）;然而，在所有检查区域中，5-羟色胺和多巴胺水平均降低。这些结果表明，BK（激肽）可能抑制脊髓伤害性感觉传递，并通过突触前作用于球脊髓含NA纤维的终末产生镇痛作用。
In the awake restrained rat the intrathecal (i.th.) administration of 8.1 pmol-8.1 nmol of bradykinin (BK) and kallidin (KD) enhanced the reaction time (RT) to a noxious radiant heat stimulus in a dose-dependent manner. The fragments BK-(1-8) and BK-(1-7) were active only at doses higher than 10 nmol and the following rank order of potency was observed: BK > KD .mchgt. BK-(1-8) > BK(1-7). The increment of tail-flick latency was greatest at 1 (BK) or 6 (KD) min and the RT returned to basal levels within 15 min post-administration. The effect of BK (81 pmol) was unaffected by the prior i.th. administration of propranolol and naloxone but was significantly potentiated by prazosin (P < 0.05). In contrast, the response to BK was significantly blocked (P < 0.05). In contrast, the response to BK was significantly blocked (P < 0.001) by phentolamine, idazoxan and yohimbine as well as by treatment with 6-hydroxydopamine (6-OHDA) at a dose of 20 .mu.g (i.th.) 1 week earlier. The latter pretreatment reduced the antinociceptive effect of i.th. tyramine (7 .mu.mol) and potentiated that to noradrenaline (NA) (0.6 nmol) (P < 0.01) while it preserved both the aninociceptive effect of neurokinin B (8 nmol) and the hyperalgestic effect of substance P (6.5 nmol). A biochemical analysis revealed that 6-OHDA treatment reduced the NA content in the lumbar spinal cord by 60% without affecting the levels of serotonin, dopamine, adrenaline or their main metabolites. There were also significant reductions in NA content in cervical (44%) and thoracic (55%) spinal cord. Pretreatment with 6-OHDA for a longer survival period (2 weeks) caused a further decrease of NA in the lumbar spinal cord (88%); however, the serotonin and dopamine levels were reduced in all regions examined. These results suggest that BK (kinins) may inhibit spinal nociceptive sensory transmission and produce analgesia by acting presynaptically on terminals of bulbospinal NA-containing fibers.