酸敏感的G蛋白偶合受體─OGR1表現在背根神經節內與痛覺相關的感覺神經元上

當組織受傷以及發炎時，局部的氫離子濃度會上升(稱為組織酸化)，並伴隨疼痛的感覺。組織酸化是造成疼痛的主要因素。VR1和ASICs家族中的ASIC3已被證實和酸引起的疼痛相關。但是剔除VR1基因或是ASIC3基因並不能抑制酸引起的疼痛。因此，酸敏感G蛋白偶合受體是否參與酸引起的痛覺是非常有趣的研究方向。酸敏感偶合受體包括OGR1、GPR4、G2A和TDAG8，他們原本被證明是溶血磷脂質(lysophospholipids)的受體。我使用反轉錄聚合酶連鎖反應(RT-PCR)以及定量聚合酶連鎖反應的檢測方法發現在小鼠中，OGR1、GPR4、G2A和TDAG8這四個基因都表現在背根神經節(dorsal root ganglion)。在這四個基因中，OGR1的基因表現量是最高的，這表示OGR1可能在感覺的反應中具有功能。我使用同位雜交法檢驗GR1基因分布在背根神經節的哪些神經元中。結果發現，在背根神經節中的小細胞有百分之三十五表現OGR1基因，而背根神經節中的大細胞有百分之二十一表現OGR1基因。因為小細胞和痛覺相關，所以OGR1的主要功能可能和痛覺相關。氫離子和sphingosylphosphatidylcholine (SPC，一種溶血磷脂質)都可以活化OGR1，使細胞內的鈣離子濃度增加，且氫離子和SPC是相互競爭的agonists。

關鍵字

G蛋白偶合受體；背根神經節；痛覺；神經科學

並列摘要

Tissue injury and inflammation often raise local proton concentration (called tissue acidosis) and accompany with painful sensations. Tissue acidosis is a dominant factor that contributes to pain. Vanilloid receptor 1 (VR1) and acid-sensing ion channel 3 (ASIC3), one member of ASIC family, are proved to be related to acid-induced pain. However, acid-induced pain is not inhibited in ASIC3 or VR1 gene deletion. Therefore it would be interesting to know whether proton-sensing GPCRs are involved in acid-induced nociception. Proton-sensing GPCRs, including ovarian cancer G-protein-coupled receptor 1 (OGR1), GPR4, G2A, and T cell death associated gene 8 (TDAG8), are originally identified as lysophospholipid receptors. Using RT-PCR and quantitative PCR, I have found that mouse OGR1, GPR4, G2A, and TDAG8 are expressed in dordal root ganglion (DRG). Among the four genes, OGR1 has the highest expression levels in DRG, suggesting that OGR1 may have a role in sensory responses. The localization of OGR1 gene in DRG neurons was examined using in situ hybridization and the results show that 35% small-diameter and 21% large-diameter neurons have OGR1 expression. Since small-diameter neurons are related to nociception, the major function of mOGR1 is probably involved in nociception. Both of proton and sphingosylphosphatidylcholine (SPC) can activate OGR1 to increase intracellular calcium concentration, and they are competitive agonists for OGR1.

並列關鍵字

dorsal root ganglion ； nociception ； pain ； neuroscience ； G-protein-coupled receptors ； OGR1

參考文獻

Alvarez-de-la Rosa, D., Zhang, P., Shao, D., White, F. and Canessa, C.M., 2002. Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. Proc. Natl. Acad. Sci. U. S. A. 99, pp. 2326–2331.

Alvarez-de-la Rosa, D., Krueger, S.R., Kolar, A., Shao, D., Fitzsimonds, R.M. and Canessa, C.M., 2003. Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system. J. Physiol. 546, pp. 77–87.

Akaike, N., Krishtal, O.A. and Maruyama, T., 1990. Proton-induced sodium current in frog isolated dorsal root ganglion cells. J. Neurophysiol. 63, pp. 805-813.

An, S., Tsai, C. and Goetzl, E.J., 1995. Cloning, sequencing and tissue distribution of two related G protein-coupled receptor candidates expressed prominently in human lung tissue. FEBS Lett. 375, pp. 121-124.

An, S., Bleu, T., Huang, W., Hallmark, O.G., Coughlin, S.R. and Goetzl, E.J., 1997. Identification of cDNAs encoding two G protein-coupled receptors for lysosphingolipids. FEBS Lett. 417, pp. 279– 282.

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酸敏感的G蛋白偶合受體─OGR1表現在背根神經節內與痛覺相關的感覺神經元上

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