酸敏感G蛋白偶合受體調節的鈣離子訊息調控急性到慢性疼痛的轉換;Proton-sensing GPCR-mediated calcium signals regulate the transition from acute to chronic pain.

NCUIR > college of Health Sciences and Technology > Graduate Institute of Life Science > Electronic Thesis & Dissertation > Item 987654321/71455

Please use this identifier to cite or link to this item: http://ir.lib.ncu.edu.tw/handle/987654321/71455

Title:	酸敏感G蛋白偶合受體調節的鈣離子訊息調控急性到慢性疼痛的轉換;Proton-sensing GPCR-mediated calcium signals regulate the transition from acute to chronic pain.
Authors:	黃雅涵;Huang,Ya Han
Contributors:	生命科學系
Keywords:	酸敏感G蛋白偶合受體;proton-sensing GPCR;TDAG8;OGR1;G2A
Date:	2016-08-31
Issue Date:	2016-10-13 13:05:16 (UTC+8)
Publisher:	國立中央大學
Abstract:	組織受傷或發炎時，局部氫離子濃度會上升，此現象稱為組織酸化，組織酸化常伴隨著疼痛的感覺，且是造成疼痛的主要因子。辣椒素受體1以及酸敏感離子通道3已經被證實與酸引起的疼痛相關，而酸敏感G蛋白偶合受體的功能還未被確定。G蛋白偶合受體的家族含有四個基因:OGR1，GPR4，G2A與TDAG8。我們之前的研究發現酸敏感偶合受體的四個基因皆有表現在背根神經節的痛覺敏感神經內，並且與辣椒素受體1以及酸敏感離子通道3都會同時表現。而TDAG8的活化會使辣椒素受體1對辣椒素的反應敏感化。在CFA藥劑引起的發炎反應中，長時的痛覺敏感受到PKA與PKC兩條訊息路徑的調控，此兩條路徑調控的時間轉換點約在注射CFA藥劑的三到四小時之後。直接注射酸所引起的急性痛覺敏感也一樣受到PKA與PKC兩條訊息路徑的調控，而兩個路徑轉換的時間點約在酸注射二到四小時之後。因此，在發炎時，此兩條調控的訊息路徑轉換可能是由酸引起的。Gs-AC-PKA 訊息路徑可能負責調控四小時前的痛覺敏感，而Gi- PLC- PKC 訊息路徑則負責四小時之後的痛覺敏感。總括來說，酸敏感偶合受體可能參與在此兩條調控的訊息路徑。此篇研究發現，注射CFA藥劑兩小時後，TDAG8在酸引起的胞內鈣離子訊息變化上具有十分重要的調控作用，對於注射CFA藥劑二十四小時後的包內鈣離子濃度變化同樣具有重要的作用。而同時表現OGR1以及G2A使得細胞對酸的敏感度增加，並同時增加胞內的鈣離子濃度。進一步發現OGR1以及G2A同時表現時，下游涉及的訊息路徑是Gi- PLC- PKC，因此OGR1與G2A的異體偶合可能涉及發炎反應中觀察到的Gi- PLC- PKC調控路徑。;Tissue injury and inflammation raise local proton concentration (called tissue acidosis) and accompany with painful sensations. Tissue acidosis is a dominant factor that contributes to pain. Transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channel 3 (ASIC3), one member of ASIC family, are proved to be related to acid-induced pain. Proton-sensing G-protein-coupled receptors (GPCRs) consists of ovarian cancer G-protein-coupled receptor 1 (OGR1), GPR4, G2A and T-cell death associated gene 8 (TDAG8). Our previous study indicates that the OGR1 family are expressed in nociceptors of DRG, and are co-localized with TRPV1 and ASIC3. TDAG8 activation sensitize TRPV1 response to capsaicin. In complete Freund’s adjuvant (CFA)-induced inflammation, prolonged hyperalgesia in mice is regulated by PKA and PKC. The switch time for PKA and PKC dependency is about 3 to 4 hours. Acute hyperalgesia induced by acidic solution (pH 5.5 or 5.0) depended on both PKA and PKC, as for prolonged hyperalgesia induced by CFA. The switch time for PKA and PKC dependency is about 2 to 4 hours. Therefore, the switch of PKA and PKC dependency in prolonged hyperalgesia induced by CFA can be due to acidosis signals. The Gs-AC-PKA pathway may be responsible for the early phase of hyperalgesia and Gi- PLC- PKC pathway for the late phase. Taken together, proton-sensing GPCRs might be the candidate to be involved in these two pathways. In this study, I have found the dominant role of TDAG8 to mediate proton-induced calcium signals after 2 hours of CFA injection, and TDAG8 is involved in the case after 24 hours of CFA injection as well. Co-expression of OGR1 and G2A increases the sensitivity to proton, and the magnitude of intracellular calcium signals. Co-expression of OGR1 and G2A is involved in a Gi- PLC- PKC pathway. OGR1 and G2A heteromer is the candidate responsible to the Gi- PLC- PKC pathway observed in inflammation.
Appears in Collections:	[Graduate Institute of Life Science] Electronic Thesis & Dissertation

Files in This Item:

File	Description	Size	Format
index.html		0Kb	HTML	427	View/Open

社群 sharing

Loading...