Characterization of μ opioid receptor binding and G protein coupling in rat hypothalamus, spinal cord, and primary afferent neurons during inflammatory pain
Characterization of μ opioid receptor binding and G protein coupling in rat hypothalamus, spinal cord, and primary afferent neurons during inflammatory pain
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DOI：
10.1124/jpet.103.057257
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发表时间：
2004-02-01
影响因子：
3.5
通讯作者：
Schäfer, M
中科院分区：
文献类型：
--
作者：
Shaqura, MA;Zöllner, C;Schäfer, M
阿片类药物的外周镇痛作用在炎症条件下（例如关节炎）很明显；然而，对于外周神经系统与中枢神经系统中 mu 阿片受体结合和 G 蛋白偶联的适应性变化知之甚少。本研究调查了炎症对μ阿片受体（MOP受体）结合以及脊髓上、脊髓和外周MOP受体的G蛋白偶联的影响。此外，在免疫组织化学实验中，在炎症和非炎症大鼠的背根神经节（DRG）中鉴定出了 MOP 受体。 MOP受体结合位点的数量从下丘脑(HT)>脊髓(SC)>DRG依次减少。一侧后爪的单侧弗氏完全佐剂炎症仅在 DRG 中诱导 MOP 受体位点显着上调，而在 HT 或 SC 中则不然。这种上调具有时间依赖性，仅限于发炎侧，并在 24 小时达到峰值。全激动剂[D-Ala(2)、N-Me-Phe(4)、Gly(5)-ol]-脑啡肽(DAMGO)诱导MOP受体G蛋白偶联，并且从HT>SC>DRG，功效(E-max)递减。炎症仅导致 DRG 膜中 MOP 受体 G 蛋白偶联显着增加，而在炎症对侧的 HT、SC 或 DRG 中则不然。这表明 MOP 受体水平的变化与全身释放的介质无关。这些发现表明，在初级传入神经元中选择性刺激 DAMGO 后，炎症会导致 MOP 受体结合和 G 蛋白偶联发生变化，但不会引起 HT 或 SC 中 MOP 受体的任何适应性变化。
Peripheral analgesic effects of opioids are pronounced under inflammatory conditions, e.g., arthritis; however, little is known about adaptive changes of mu opioid receptor binding and G protein coupling in the peripheral versus central nervous system. The present study investigated the effects of inflammation on mu opioid receptor (MOP receptor) binding and G protein coupling of supraspinal, spinal, and peripheral MOP receptors. In addition, MOP receptors were identified in immunohistochemical experiments in dorsal root ganglia (DRG) of inflamed and noninflamed rats. The number of MOP receptor binding sites decreased from hypothalamus (HT) > spinal cord (SC) > DRG. Unilateral Freund's complete adjuvant inflammation of one hindpaw induced a significant up-regulation of MOP receptor sites only in DRG but not in HT or SC. This up-regulation was time-dependent, restricted to the inflamed side, and showed a peak at 24 h. The full-agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO) induced MOP receptor G protein coupling with decreasing efficacies (E-max) from HT > SC > DRG. Inflammation resulted in significant increases in MOP receptor G protein coupling only in membranes of DRG, but not in HT, SC, or DRG on the contralateral side of inflammation. This suggests that changes in MOP receptor levels are not related to systemically released mediators. These findings show that inflammation causes changes in MOP receptor binding and G protein coupling after DAMGO stimulation selectively in primary afferent neurons but did not cause any adaptive changes of MOP receptor in HT or SC.