組織的受損與發炎，往往引起局部組織中氫離子濃度的增加，造成組織酸化。組織酸化被認為是導致疼痛的主要原因，目前已知有兩個陽離子通道，酸敏感離子通道家族(acid-sensing ion channel；ASIC3)及辣椒素受體（vanilloid receptor 1；VR1），可以受到氫離子的活化，並且參與傷害感受覺（nociception）的傳遞。最近的研究發現，屬於酸敏感G 蛋白偶合受體（proton-sensing G-protein-coupledreceptors）的OGR1 接受體家族，也可以接收氫離子的刺激，包括了：OGR1、GPR4 、TDAG8 及G2A。G2A 在早期認為是LPC（ 脫脂磷酸脂膽鹼，lysophosphatidylcholine ） 的接受體， 並且受到氫離子及9-HODE（9-hydroxyoctadecadienoic）的活化。然而，G2A 是否可被氫離子所活化，並且是否參與傷害感受覺的調控機制，仍然不清楚。本篇論文的主要目的，是在探討氫離子對於G2A 的影響以及表現形式。經由RT-PCR 的結果顯示，G2A 在許多組織中均有表現，包括了背根神經節（dorsal root ganglia；DRG）。G2A 主要表現在小直徑，IB4-positive 的傷害感受器（nociceptor）。其中有趣的是，G2A 增加表現量在ASIC3 基因剔除小鼠DRG 中，並且主要增加在大直徑細胞。因此，G2A 也許參與了傷害感受覺的調控。然而在氫離子對G2A 的影響方面，與前人的實驗結果相符，我發現G2A 無法被氫離子所活化。 Tissue injury and inflammation often cause an increase of hydrogen ion concentration in local tissues, called tissue acidosis. Tissue acidosis seems to be the dominant factor that leads to painful sensation. Two cation channels,acid-sensing ion channel(ASIC3) and vanilloid receptor 1, are activated by proton and involved in nociceptive transduction. Recently, a subfamily of G-protein-coupled receptor (GPCR) including OGR1, GPR4, TDAG8 and G2A has been identified as proton-sensing receptors. G2A is originally known as a lysophosphatidylcholine (LPC) receptor and is also actived by proton and 9-hydroxyoctadecadienoic. However, original studies for LPC and proton cannot be reproducible. Whether G2A is activated by proton and whether it is involved in nociception remain unclear. The objective of this thesis is to determine effects of pH on G2A and study its expression pattern. From RT-PCR results, G2A was expressed in many tissues including dorsal root ganglia (DRG). G2A was predominantly expressed in small-diameter, IB4-positive nociceptors. Interestingly, expression levels of G2A increased in ASIC3-/-DRG. This increase is due to an increase in G2A-expressing neurons, mainly in large diameter neurons. Accordingly, G2A may be involved in nociception. Consistent with previous studies, I have found G2A cannot be activated by proton.
