酸敏感G蛋白偶合受體OGR1, G2A, GPR4經由不同方式調控發炎所產生的機械性痛覺敏感現象

簡易檢索 / 詳目顯示

回結果列表

研究生：	黃真 Jen Wong
論文名稱：	酸敏感G蛋白偶合受體OGR1, G2A, GPR4經由不同方式調控發炎所產生的機械性痛覺敏感現象 OGR1, G2A, and GPR4 regulate mechanical hyperalgesia induced by inflammation via distinct ways
指導教授：	孫維欣 Wei-Hsin Sun
口試委員:
學位類別：	碩士 Master
系所名稱：	生醫理工學院 - 生命科學系 Department of Life Science
論文出版年：	2017
畢業學年度：	106
語文別：	英文
論文頁數：	79
中文關鍵詞：	酸敏感性G蛋白耦合受體、完全弗氏佐劑
外文關鍵詞：	GPR4
相關次數：	點閱：13 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

長期發炎性疼痛主要是發炎反應產生時會釋放發炎相關介質，其會活化或調控傷害感受器，導致疼痛和痛覺敏感的現象產生。發炎介質中的酸會造成組織酸化，其為引發疼痛的重要因素。有二類酸敏性受體，一是酸敏感性離子通道，另一個則是酸敏感性G蛋白耦合受體。酸敏感性G蛋白耦合受體，包含OGR1、 GPR4、 G2A和TDAG8，可以表現在小直徑的痛覺神經中。TDAG8在注射CFA後1天表現量會增加，而G2A則是在90分鐘時增多。將TDAG8基因表現量降低可以延遲CFA所誘導的痛覺敏感現象，而過度表現G2A則可以降低CFA所引起的早期的痛覺敏感現象。這些研究指出TDAG8可能有促進疼痛的角色，而G2A則是有抑制疼痛的角色。然而，目前其它酸敏感性G蛋白耦合受體在發炎性疼痛中所扮演的角色仍然不清楚。為了解決這個問題，我的實驗中使用short-hairpin RNA (shRNA)來抑制酸敏感性G蛋白耦合受體的基因，探討他們在疼痛上的角色。我發現抑制OGR1會在CFA注射後4小時減緩機械性痛覺敏感現象，並且減少粒細胞的數量。而抑制G2A除延長機械性痛覺敏感現象外，另會在42天增加粒細胞的數量。抑制GPR4雖會延長痛覺敏感現象，但並不會改變免疫細胞數量的變化。

Chronic inflammatory pain results from inflammation that releases the mediators to activate or modulate the nociceptors, leading to pain and hyperalgesia. Tissue acidosis appears to be a dominant factor in inflammatory pain, and the acidosis signals can be sensed by the proton-sensing ion channels and G proton-coupled receptors (GPCRs). The proton-sensing GPCRs, Ovarian cancer G protein-coupled receptor 1 (OGR1), G protein-coupled receptor 4 (GPR4), G2 accumulation (G2A), and T-cell death associated gene 8 (TDAG8), were found in small-diameter nociceptors, and TDAG8 expression was increased at 1 day, while G2A expression increased at 90 minutes after CFA inflammation. The inhibition of TDAG8 delays the onset of CFA-induced hyperalgesia, whereas overexpression of G2A reduced hyperalgesia at the early phase. These results suggested that TDAG8 may have a pro-nociceptive role, and G2A have an anti-nociceptive role in CFA-induced hyperalgesia. However, the roles of other proton-sensing GPCRs in inflammatory pain are still unclear. To address this issue, proton-sensing GPCRs were knocked down with short hairpin RNA. I have found that OGR1 knockdown mice significantly reduced mechanical hyperalgesia and decreased the number of granulocytes at 4 hours after CFA injection. Moreover, knockdown of G2A prolonged mechanical hyperalgesia and increased the number of granulocytes at 42 days, whereas GPR4 knockdown mice prolonged hyperalgesia but did not change the number of immune cells.

中文摘要i
Abstract ii
Acknowledgements iii
Table of Contents iv
List of Figures vii
List of Tables viii

Table of Contents
Chapter 1 Introduction 1
1.1. Pain 2
1.2 Inflammatory pain 3
1.3 Tissue Acidosis 5
1.4 Proton-sensing receptors 5
1.4.1 Proton-sensing G protein-coupled Receptors 6
1.4.1.1 Ovarian cancer G protein-coupled receptor 1 (OGR1) 6
1.4.1.2 G2 accumulation (G2A) 7
1.4.1.3 G protein-coupled receptor 4 (GPR4) 8
1.4.1.4 T cell death-associated gene 8 (TDAG8) 9
1.5 Research purpose 10
Chapter 2 Materials and methods 11
2.1 Materials 12
2.1.1 Experimental bacterial strains and animals 12
2.1.2 Agents and Chemicals 12
2.1.3 Plasmids (RNA interference) 13
2.2 Methods 13
2.2.1 Amplification and purification of plasmid 13
2.2.1.1 Bacterial transformation 13
2.2.1.2 Mini preparation 13
2.2.1.3 Midi preparation 14
2.2.2 Subcloning of shRNA 15
2.2.2.1 Preparation of vectors 15
2.2.2.2 Preparation of inserts 15
2.2.2.3 Preparation of inserts 16
2.2.3 Animal experiments 16
2.2.3.1 Inflammatory pain model 16
2.2.3.2 Behavioral tests 16
2.2.4 Immunohistochemistry 17
2.2.4.1 Slides preparation 17
2.2.4.2 Tissue collection and sectioning 17
2.2.4.3 Immunostaining 17
2.2.5 Hematoxylin and Eosin staining 18
2.2.6 Data analysis 19
Chapter 3 Results 20
3.1 Cloning map of shTDAG8-B1, shOGR1-26108, shG2A-27458, shG2A-27477, and shGPR4-28164 21
3.2 Intraplantar injection of CFA induces long-term mechanical hyperalgesia in ICR and C57BL/6 mice 21
3.3 Intraplantar injection of CFA induces mechanical hyperalgesia and inflammation in cherry vector-treated mice 22
3.4 Knockdown of OGR1 can reduce CFA-induced mechanical hyperalgesia and decreases granulocytes at 4 hours 23
3.5 Knockdown with shG2A-27477 prolongs CFA-induced inflammatory pain and increases granulocytes at day 42, and knockdown with shG2A-27458 is not effective in CFA inflammatory pain and inflammation 24
3.6 Knockdown of GPR4 prolongs CFA-induced mechanical hyperalgesia but does not enhance inflammation at day 42 27
3.7 Knockdown and knockout of TDAG8 reduces pain CFA-induced mechanical hyperalgesia 28
Chapter 4 Discussion 30
4.1 Long-term mechanical hyperalgesia induced by CFA 31
4.2 Changes in immune cell numbers during inflammatory pain 32
4.3 Inhibition of OGR1 reduces CFA-induced mechanical hyperalgesia and decreases number of granulocytes at 4 hours 32
4.4 Knockdown with shG2A-27477 prolongs CFA-induced mechanical hyperalgesia, and knockdown with shG2A-27458 is not effective in inflammatory pain 33
4.5 Inhibition of GPR4 prolongs CFA-induced hyperalgesia but doesn’t enhance inflammation 35
4.6 Inhibition of TDAG8 reduces hyperalgesia and shortens inflammatory hyperalgesia 36
4.7 Conclusion 37
Chapter 5 References 38
Appendix 65

List of Figures
Figure 3.1 The maps of shRNA constructs 46
Figure 3.2 CFA injection induces mechanical hyperalgesia in ICR and C57BL/6 wild-type mice 47
Figure 3.3 CFA injection induces mechanical hyperalgesia in vector-injected mice 48
Figure 3.4 CFA injection induces immune cell infiltration in vector-injected mice 49
Figure 3.5 Knockdown of OGR1 reduces CFA-induced inflammatory pain at 240 minutes 50
Figure 3.6 Knockdown of OGR1 decreases number of granulocytes at 4 hours after CFA injection 51
Figure 3.7 Knockdown with shG2A-27477 prolongs mechanical hyperalgesia, while knockdown with shG2A-27458 does not affect mechanical hyperalgesia 53
Figure 3.8 Knockdown with shG2A-27477 enhances inflammation at 42 days 54
Figure 3.9 Knockdown with shG2A-27458 does not change the number of immune cells at 28 days 55
Figure 3.10 Knockdown of GPR4 prolongs CFA-induced mechanical hyperalgesia 56
Figure 3.11 Knockdown of GPR4 does not change the number of immune cells at 42 days 57
Figure 3.12 Knockdown and knockout of TDAG8 significantly reduces CFA-induced inflammatory pain 58

List of Tables
Table 2.1 Information of shRNA plasmids 59
Table 3.1 The number of immune cells in vector-injected paws 60
Table 3.2 The number of immune cells in shOGR1-26108-injected paws 61
Table 3.3 The number of immune cells in shG2A-27477-injected paws 62
Table 3.4 The number of immune cells in shG2A-27458-injected paws 63
Table 3.5 The number of immune cells in shGPR4-28164-injected paws 64

                                

Aoki H, Mogi C, Hisada T, Nakakura T, Kamide Y, Ichimonji I, Tomura H, Tobo M, Sato K, Tsurumaki H, Dobashi K, Mori T, Harada A, Yamada M, Mori M, Ishizuka T, Okajima F. (2013) Proton-sensing ovarian cancer G protein-coupled receptor 1 on dendritic cells is required for airway responses in a murine asthma model. PLoS One. 8(11):e79985.

Bolick DT, Whetzel AM, Skaflen M, Deem TL, Lee J, Hedrick CC. (2007) Absence of the G Protein–Coupled Receptor G2A In Mice Promotes Monocyte/Endothelial Interactions in Aorta. Circ. Res. 100(4):572-80.

Brooks J, Tracey I. (2005) From nociception to pain perception: imaging the spinal and supraspinal pathways. J Anat. 207(1):19-33.

Chen YJ, Huang CW, Lin CS, Chang WH, Sun WH. (2009) Expression and function of proton-sensing G-protein-coupled receptors in inflammatory pain. Mol Pain. 5:39.

Chen A, Dong L, Leffler NR, Asch AS, Witte ON, Yang LV. (2011) Activation of GPR4 by acidosis increases endothelial cell adhesion through the cAMP/Epac pathway. PLoS One. 6(11):e27586.

Choi JW, Lee SY, Choi Y. (1996) Identification of a putative G protein-coupled receptor induced during activation-induced apoptosis of T cells. Cell Immunol. 168(1):78-84.

Costigan M, Scholz J, Woolf CJ. (2009) Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 32:1-32.

Cunha TM, Verri WA Jr, Schivo IR, Napimoga MH, Parada CA, Poole S, Teixeira MM, Ferreira SH, Cunha FQ. (2008) Crucial role of neutrophils in the development of mechanical inflammatory hypernociception. J Leukoc Biol. 83(4):824-32.

D'Souza CA, Zhao FL, Li X, Xu Y, Dunn SE, Zhang L. (2016) OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages. PLoS One. 11(2):e0148439.

da Costa DS, Meotti FC, Andrade EL, Leal PC, Motta EM, Calixto JB. (2010) The involvement of the transient receptor potential A1 (TRPA1) in the maintenance of mechanical and cold hyperalgesia in persistent inflammation. Pain. 148(3):431-7.

de Vallière C, Wang Y, Eloranta JJ, Vidal S, Clay I, Spalinger MR, Tcymbarevich I, Terhalle A, Ludwig MG, Suply T, Fried M, Kullak-Ublick GA, Frey-Wagner I, Scharl M, Seuwen K, Wagner CA, Rogler G. (2015) G Protein-coupled pH-sensing Receptor OGR1 Is a Regulator of Intestinal Inflammation. Inflamm Bowel Dis. 21(6):1269-81.

Dong L, Li Z, Leffler NR, Asch AS, Chi JT, Yang LV. (2013) Acidosis activation of the proton-sensing GPR4 receptor stimulates vascular endothelial cell inflammatory responses revealed by transcriptome analysis. PLoS One. 8(4):e61991.

Dong L., Li Z., Yang L. (2014) Function and Signaling of the pH-Sensing G Protein-Coupled Receptors in Physiology and Diseases. In: Chi JT. (eds) Molecular Genetics of Dysregulated pH Homeostasis. pp 45-65

Dubin AE, Patapoutian A. (2010) Nociceptors: the sensors of the pain pathway. J Clin Invest. 120(11): 3760–3772.

Gao YJ, Xu ZZ, Liu YC, Wen YR, Decosterd I, Ji RR. (2010) The c-Jun N-terminal kinase 1 (JNK1) in spinal astrocytes is required for the maintenance of bilateral mechanical allodynia under a persistent inflammatory pain condition. Pain. 148(2):309-19.

Ghasemlou N, Chiu IM, Julien JP, Woolf CJ. (2015) CD11b+Ly6G- myeloid cells mediate mechanical inflammatory pain hypersensitivity. Proc Natl Acad Sci USA. 112(49):E6808-17.

Gu Q, Lee LY. (2010) Acid-Sensing Ion Channels and Pain. Pharmaceuticals (Basel). 3(5):1411-1425.

Frasch SC, Berry KZ, Fernandez-Boyanapalli R, Jin HS, Leslie C, Henson PM, Murphy RC, Bratton DL. (2008) NADPH oxidase-dependent generation of lysophosphatidylserine enhances clearance of activated and dying neutrophils via G2A. J Biol Chem. 283(48):33736-49.

Frasch SC, Fernandez-Boyanapalli RF, Berry KZ, Leslie CC, Bonventre JV, Murphy RC, Henson PM, Bratton DL. (2011) Signaling via macrophage G2A enhances efferocytosis of dying neutrophils by augmentation of Rac activity. J Biol Chem. 286(14):12108-22.

Frasch SC, McNamee EN, Kominsky D, Jedlicka P, Jakubzick C, Berry KZ, Mack M, Furuta GT, Lee JJ, Henson PM, Colgan SP, Bratton DL. (2016) G2A signaling dampens colitic inflammation via production of IFNγ. J Immunol. 197(4): 1425–1434.
Hang LH, Yang JP, Yin W, Wang LN, Guo F, Ji FH, Shao DH, Xu QN, Wang XY, Zuo JL. (2012) Activation of spinal TDAG8 and its downstream PKA signaling pathway contribute to bone cancer pain in rats. European Journal of Neuroscience. 36(1):2107-17.

He XD, Tobo M, Mogi C, Nakakura T, Komachi M, Murata N, Takano M, Tomura H, Sato K, Okajima F. (2011) Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages. Biochem Biophys Res Commun. 415(4):627-31.

Holzer P. (2009) Acid-sensitive ion channels and receptors. Handb Exp Pharmacol. (194):283-332.

Huang CW, Tzeng JN, Chen YJ, Tsai WF, Chen CC, Sun WH. (2007) Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors. Mol Cell Neurosci. 36(2):195-210.

Huang WY, Dai SP, Chang YC, Sun WH. (2015) Acidosis Mediates the Switching of Gs-PKA and Gi-PKCε Dependence in Prolonged Hyperalgesia Induced by Inflammation. PLoS One. 10(5):e0125022.

Huang YF. (2015) Deletion of ASIC3 and TRPV1 gene shortens chronic mechanical hyperalgesia induced by inflammation.

Ichimonji I, Tomura H, Mogi C, Sato K, Aoki H, Hisada T, Dobashi K, Ishizuka T, Mori M, Okajima F. (2010) Extracellular acidification stimulates IL-6 production and Ca (2+) mobilization through proton-sensing OGR1 receptors in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 299(4):L567-77.

Ishii S, Kihara Y, Shimizu T. (2005) Identification of T cell death-associated gene 8 (TDAG8) as a novel acid sensing G-protein-coupled receptor.J Biol Chem. 280(10):9083-7.

Ji RR, Xu ZZ, Gao YJ. (2014) Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov. 13(7):533-48.

Ji RR, Chamessian A, Zhang YQ. (2016) Pain Regulation by Non-neuronal Cells and Inflammation. Science. 354(6312): 572–577.

Julius D, Basbaum AI. (2001) Molecular mechanisms of nociception. Nature. 413(6852):203-10.

Justus CR, Dong L, Yang LV. (2013) Acidic tumor microenvironment and pH-sensing G protein-coupled receptors. Front Physiol. 4:354.

Kabarowski JH. 2009 G2A and LPC: regulatory functions in immunity. Prostaglandins Other Lipid Mediat. 89(3-4):73-81.

Kidd BL, Urban LA. (2001) Mechanisms of inflammatory pain. Br J Anaesth. 87(1):3-11.

Kumar NN, Velic A, Soliz J, Shi Y, Li K, Wang S, Weaver JL, Sen J, Abbott SB, Lazarenko RM, Ludwig MG, Perez-Reyes E, Mohebbi N, Bettoni C, Gassmann M, Suply T, Seuwen K, Guyenet PG, Wagner CA, Bayliss DA. (2015) Regulation of breathing by CO₂ requires the proton-activated receptor GPR4 in retrotrapezoid nucleus neurons. Science. 348(6240):1255-60.

Kyaw H, Zeng Z, Su K, Fan P, Shell BK, Carter KC, Li Y. (1998) Cloning, characterization, and mapping of human homolog of mouse T-cell death-associated gene. DNA Cell Biol. 17(6):493-500.

Lavich TR, Siqueira Rde A, Farias-Filho FA, Cordeiro RS, Rodrigues e Silva PM, Martins MA. (2006) Neutrophil infiltration is implicated in the sustained thermal hyperalgesic response evoked by allergen provocation in actively sensitized rats. Pain. 125(1-2):180-7.

Li H, Wang D, Singh LS, Berk M, Tan H, Zhao Z, Steinmetz R, Kirmani K, Wei G, Xu Y. (2009) Abnormalities in osteoclastogenesis and decreased tumorigenesis in mice deficient for ovarian cancer G protein-coupled receptor 1. PLoS One. 4(5):e5705.

Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, Hofstetter H, Wolf RM, Seuwen K. (2003) Proton-sensing G-protein-coupled receptors. Nature. 425(6953):93-8.

Lum H, Qiao J, Walter RJ, Huang F, Subbaiah PV, Kim KS, Holian O. (2003) Inflammatory stress increases receptor for lysophosphatidylcholine in human microvascular endothelial cells. Am J Physiol Heart Circ Physiol. 285(4):H1786-9.

Mahadevan MS, Baird S, Bailly JE, Shutler GG, Sabourin LA, Tsilfidis C, Neville CE, Narang M, Korneluk RG. (1995) Isolation of a novel G protein-coupled receptor (GPR4) localized to chromosome 19q13.3. Genomics. 30(1):84-8.
Marchand F, Perretti M, McMahon SB. (2005) Role of the immune system in chronic pain. Nat Rev Neurosci. 6(7):521-32.

Metcalf D, Robb L, Dunn AR, Mifsud S, Di Rago L. (1996) Role of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in the development of an acute neutrophil inflammatory response in mice. Blood. 88(10):3755-64.

Mogi C, Tobo M, Tomura H, Murata N, He XD, Sato K, Kimura T, Ishizuka T, Sasaki T, Sato T, Kihara Y, Ishii S, Harada A, Okajima F. (2009) Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages. J Immunol. 182(5):3243-51.

Morriello F. (2016) Neutrophils and Inflammation: Unraveling a New Connection. Biol Med (Aligarh) 8:325.

Murakami N, Yokomizo T, Okuno T, Shimizu T. (2004) G2A is a proton-sensing G-protein-coupled receptor antagonized by lysophosphatidylcholine. J Biol Chem. 279(41):42484-91.

Okajima F. (2013) Regulation of inflammation by extracellular acidification and proton-sensing GPCRs. Cell Signal. 25(11):2263-71.

Onozawa Y, Komai T, Oda T. (2011) Activation of T cell death-associated gene 8 attenuates inflammation by negatively regulating the function of inflammatory cells. Eur J Pharmacol. 654(3):315-9.

Pereverzev A, Komarova SV, Korcok J, Armstrong S, Tremblay GB, Dixon SJ, Sims SM. (2008) Extracellular acidification enhances osteoclast survival through an NFAT-independent, protein kinase C-dependent pathway. Bone. 42(1):150-61.

Pinho-Ribeiro FA, Verri WA Jr, Chiu IM. (2017) Nociceptor Sensory Neuron-Immune Interactions in Pain and Inflammation. Trends Immunol. 38(1):5-19.

Radu CG, Nijagal A, McLaughlin J, Wang L, Witte ON. (2005) Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells. Proc Natl Acad Sci USA. 102(5):1632-7.

Reeh PW, Steen KH. (1996) Tissue acidosis in nociception and pain. Prog Brain Res. 113:143-51.

Ren K, Dubner R. (2010) Interactions between the immune and nervous systems in pain. Nat Med. 16(11):1267-76.

Sanderlin EJ, Justus CR, Krewson EA, Yang LV. (2015) Emerging roles for the pH-sensing G protein-coupled receptors in response to acidotic stress. Cell Health and Cytoskeleton. 2015:(7) 99-109

Sanderlin EJ, Leffler NR, Lertpiriyapong K, Cai Q, Hong H, Bakthavatchalu V, Fox JG, Oswald JZ, Justus CR, Krewson EA, O'Rourke D, Yang LV. (2017) GPR4 deficiency alleviates intestinal inflammation in a mouse model of acute experimental colitis. Biochim Biophys Acta. 1863(2):569-584.

Scholz J, Woolf CJ. (2002) Can we conquer pain? Nat Neurosci. Suppl:1062-7.

Steen KH1, Reeh PW, Anton F, Handwerker HO. (1992) Protons selectively induce lasting excitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro. J Neurosci. 12(1):86-95.

Steen KH, Steen AE, Reeh PW. (1995) A dominant role of acid pH in inflammatory excitation and sensitization of nociceptors in rat skin, in vitro. J Neurosci. 15(5)3982-3989

Steen KH, Steen AE, Kreysel HW, Reeh PW. (1996) Inflammatory mediators potentiate pain induced by experimental tissue acidosis. Pain. 66(2-3):163-70.

Su YS, Sun WH, Chen CC. (2014) Molecular mechanism of inflammatory pain. World J Anesthesiol. 3(1): 71-81

Sun WH, Chen CC. (2016) Roles of Proton-Sensing Receptors in the Transition from Acute to Chronic Pain. J Dent Res. 95(2):135-42.

Tappe-Theodor A, Constantin CE, Tegeder I, Lechner SG, Langeslag M, Lepcynzsky P, Wirotanseng RI, Kurejova M, Agarwal N, Nagy G, Todd A, Wettschureck N, Offermanns S, Kress M, Lewin GR, Kuner R. (2012) Gα(q/11) signaling tonically modulates nociceptor function and contributes to activity-dependent sensitization. Pain. 153(1):184-96.

Thomas RM, Schmedt C, Novelli M, Choi BK, Skok J, Tarakhovsky A, Roes J. (2004) C-terminal SRC kinase controls acute inflammation and granulocyte adhesion. Immunity. 20(2):181-91.

Tomura H, Wang JQ, Komachi M, Damirin A, Mogi C, Tobo M, Kon J, Misawa N, Sato K, Okajima F. (2005) Prostaglandin I2 production and cAMP accumulation in response to acidic extracellular pH through OGR1 in human aortic smooth muscle cells. J Biol Chem. 280(41):34458-64.

Velcicky J, Miltz W, Oberhauser B, Orain D, Vaupel A, Weigand K, Dawson King J, Littlewood-Evans A, Nash M, Feifel R, Loetscher P. (2017) Development of Selective, Orally Active GPR4 Antagonists with Modulatory Effects on Nociception, Inflammation, and Angiogenesis. J Med Chem. 60(9):3672-3683.

Wang JQ, Kon J, Mogi C, Tobo M, Damirin A, Sato K, Komachi M, Malchinkhuu E, Murata N, Kimura T, Kuwabara A, Wakamatsu K, Koizumi H, Uede T, Tsujimoto G, Kurose H, Sato T, Harada A, Misawa N, Tomura H, Okajima F. (2004) TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor. J Biol Chem. 279(44):45626-33.

Weng Z, Fluckiger AC, Nisitani S, Wahl MI, Le LQ, Hunter CA, Fernal AA, Le Beau MM, Witte ON. (1998) A DNA damage and stress inducible G protein-coupled receptor blocks cells in G2/M. Proc Natl Acad Sci U S A. 95(21):12334-9.

Woolf CJ. (2010) What is this thing called pain? J Clin Invest. 120(11): 3742–3744.

Xu Y, Casey G. (1996) Identification of human OGR1, a novel G protein-coupled receptor that maps to chromosome 14. Genomics. 35(2):397-402.

Yan L, Singh LS, Zhang L, Xu Y. (2014) Role of OGR1 in myeloid-derived cells in prostate cancer. Oncogene. 33(2):157-64.

Yang LV, Radu CG, Roy M, Lee S, McLaughlin J, Teitell MA, Iruela-Arispe ML, Witte ON. (2007) Vascular abnormalities in mice deficient for the G protein-coupled receptor GPR4 that functions as a pH sensor. Mol Cell Biol. 27(4):1334-47.

簡易檢索 / 詳目顯示

相關論文