Taiwo Y O, Heller P H, Levine J D
Department of Anatomy, University of California, San Francisco 94143-0724.
Neuroscience. 1990;39(2):523-31. doi: 10.1016/0306-4522(90)90288-f.
Specific prostaglandins have been identified that mediate the sympathetic postganglionic neuron-terminal dependent hyperalgesia induced by bradykinin and norepinephrine, prostaglandin E2 and prostacyclin, respectively. In this study we evaluated the hypothesis that bradykinin and norepinephrine stimulate prostaglandin production in the rat, via distinct phospholipases. We found that, in normal skin, bradykinin hyperalgesia is inhibited by the phospholipase A2 inhibitor, mepacrine, but not by the phospholipase C inhibitor, neomycin and is mimicked by phospholipase A2. In chloroform-treated skin or when co-injected with A23187, bradykinin-induced hyperalgesia was found to consist of two components, one resulting from prostaglandin E2 synthesis (phospholipase A2-dependent) and one resulting from prostacyclin synthesis (phospholipase C-dependent). This latter component is blocked by Quin 2 and verapamil and also inhibited by yohimbine, an alpha 2 receptor antagonist. Arachidonic acid induces a dose-dependent hyperalgesia that was found to be like bradykinin-hyperalgesia in untreated skin (prostaglandin E2-mediated and phospholipase A2-dependent). In chloroform-treated skin or in the presence of A23187, arachidonic acid like bradykinin led to the production of prostacyclin as well as prostaglandin E2. Norepinephrine does not produce hyperalgesia in untreated skin, but in chloroform pretreated skin or in the presence of the calcium ionophore A23187, norepinephrine produces a potent dose-dependent hyperalgesia. This hyperalgesia is prevented by sympathectomy and suppressed by the calcium antagonists Quin 2 and verapamil. It is also suppressed by indomethacin and neomycin but not by SC19220 and mepacrine and is mimicked by phospholipase C.(ABSTRACT TRUNCATED AT 250 WORDS)
已鉴定出特定的前列腺素，它们分别介导由缓激肽和去甲肾上腺素诱导的交感神经节后神经元终末依赖性痛觉过敏，即前列腺素E2和前列环素。在本研究中，我们评估了以下假设：缓激肽和去甲肾上腺素通过不同的磷脂酶刺激大鼠体内前列腺素的产生。我们发现，在正常皮肤中，磷脂酶A2抑制剂米帕林可抑制缓激肽引起的痛觉过敏，但磷脂酶C抑制剂新霉素则不能，且磷脂酶A2可模拟这种作用。在氯仿处理的皮肤中或与A23187共同注射时，发现缓激肽诱导的痛觉过敏由两个成分组成，一个是由前列腺素E2合成引起的（依赖磷脂酶A2），另一个是由前列环素合成引起的（依赖磷脂酶C）。后一种成分被喹碘方和维拉帕米阻断，也被α2受体拮抗剂育亨宾抑制。花生四烯酸诱导剂量依赖性痛觉过敏，发现在未处理的皮肤中与缓激肽引起的痛觉过敏相似（由前列腺素E2介导且依赖磷脂酶A2）。在氯仿处理的皮肤中或在A23187存在的情况下，花生四烯酸与缓激肽一样导致前列环素以及前列腺素E2的产生。去甲肾上腺素在未处理的皮肤中不会产生痛觉过敏，但在氯仿预处理的皮肤中或在钙离子载体A23187存在的情况下，去甲肾上腺素会产生强效的剂量依赖性痛觉过敏。这种痛觉过敏可通过交感神经切除术预防，并被钙拮抗剂喹碘方和维拉帕米抑制。它也被吲哚美辛和新霉素抑制，但不被SC19220和米帕林抑制，且可被磷脂酶C模拟。（摘要截短于250字）
