Sex hormones regulate the contribution of PKCε and PKA signalling in inflammatory pain in the rat
Sex hormones regulate the contribution of PKCε and PKA signalling in inflammatory pain in the rat
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DOI：
10.1046/j.0953-816x.2001.01614.x
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发表时间：
2001-06-01
影响因子：
3.4
通讯作者：
Levine, JD
中科院分区：
文献类型：
--
作者：
Dina, OA;Aley, KO;Levine, JD
我们已经评估了第二信使信号的差异对炎症性疼痛的性别差异及其性激素控制的贡献。在正常雄性而非雌性大鼠中，蛋白激酶C β（PKC β）、蛋白激酶A（PKA）和一氧化氮合成酶（NOS）抑制剂可拮抗肾上腺素诱导的机械性痛觉过敏。同样，在PKC β基因敲除小鼠中，PKC β对肾上腺素依赖性机械性痛觉过敏的贡献仅发生在雄性中。相比之下，前列腺素E-2诱导的痛觉过敏，在女性和男性，依赖于PKA和NO。在两种性别，有丝分裂原活化蛋白激酶/细胞外信号相关激酶激酶（MEK）抑制剂抑制肾上腺素痛觉过敏。在性腺切除的女性，肾上腺素痛觉过敏的第二信使的贡献证明了在男性中看到的模式。给切除性腺的雌性动物施用雌激素完全重建了正常雌性动物的表型。这些数据表明，肾上腺素诱导的痛觉过敏中PKC epsilon、PKA和NO信号传导存在性别差异，这些痛觉过敏是雌激素依赖性的，并且似乎在β-肾上腺素能受体或与其偶联的G蛋白水平上发挥作用。
We have evaluated the contribution of differences in second messenger signalling to sex differences in inflammatory pain and its control by sex hormones. In normal male but not female rats, epinephrine-induced mechanical hyperalgesia was antagonized by inhibitors of protein kinase C epsilon (PKC epsilon), protein kinase A (PKA) and nitric oxide synthetase (NOS). Similarly, in PKC epsilon knockout mice, a contribution of PKC epsilon to epinephrine-dependent mechanical hyperalgesia occurred in males only. In contrast, hyperalgesia induced by prostaglandin E-2, in both females and males, was dependent on PKA and NO. In both sexes, inhibitors of mitogen-activated protein kinase/extracellular-signal related kinase kinase (MEK) inhibited epinephrine hyperalgesia. In gonadectomized females, the second messenger contributions to epinephrine hyperalgesia demonstrated the pattern seen in males. Administration of oestrogen to gonadectomized females fully reconstituted the phenotype of the normal female. These data demonstrate gender differences in PKC epsilon, PKA and NO signalling in epinephrine-induced hyperalgesia which are oestrogen dependent and appear to be exerted at the level of the beta -adrenergic receptor or the G-protein to which it is coupled.