Acid sensing by visceral afferent neurones

Acta Physiologica

Volumn 201, Issue 1, 2011, Pages 63-75

  Holzer, P ^a  

^a MEDICAL UNIVERSITY OF GRAZ   (Austria)

Author keywords

Acid induced pain; Acid sensing ion channels; Inflammation; Primary afferent neurones; Proton gated currents; TRP ion channels

Indexed keywords

ACID SENSING ION CHANNEL; EPITHELIAL SODIUM CHANNEL; G PROTEIN COUPLED RECEPTOR; POLYCYSTIN 2; POTASSIUM CHANNEL; PURINERGIC P2X RECEPTOR; TRANSIENT RECEPTOR POTENTIAL CHANNEL 4; TRANSIENT RECEPTOR POTENTIAL CHANNEL 5; VANILLOID RECEPTOR 1; VANILLOID RECEPTOR 4;

ACIDITY; ACIDOSIS; ESOPHAGUS PAIN; FEEDBACK SYSTEM; GASTROINTESTINAL PAIN; HOMEOSTASIS; HUMAN; INFLAMMATION; NONHUMAN; PAIN; PERITONEAL CAVITY; PRIORITY JOURNAL; REVIEW; SENSORY NERVE; STOMACH PAIN; UPREGULATION;

ACIDOSIS; ANIMALS; GASTRIC ACID; HOMEOSTASIS; HUMANS; HYDROGEN-ION CONCENTRATION; INFLAMMATION; INTESTINES; ION CHANNELS; NEURONS, AFFERENT; PAIN; PROTONS; RECEPTORS, G-PROTEIN-COUPLED; VISCERAL AFFERENTS;

EID: 78650047802     PISSN: 17481708     EISSN: 17481716     Source Type: Journal    
DOI: 10.1111/j.1748-1716.2010.02143.x     Document Type: Review

References (117)

1. Aihara, E., Hayashi, M., Sasaki, Y., Kobata, A. & Takeuchi, K. 2005. Mechanisms underlying capsaicin-stimulated secretion in the stomach: comparison with mucosal acidification. J Pharmacol Exp Ther 315, 423-432.
2. Akiba, Y. & Kaunitz, J.D. 2009. Luminal chemosensing and upper gastrointestinal mucosal defenses. Am J Clin Nutr 90, 826S-831S.
3. Akiba, Y., Takeuchi, T., Mizumori, M., Guth, P.H., Engel, E. & Kaunitz, J.D. 2006a. TRPV-1 knockout paradoxically protects mouse gastric mucosa from acid/ethanol-induced injury by upregulating compensatory protective mechanisms. Gastroenterology 130(Suppl. 2), A-106.
4. 2 in rat duodenum. Gastroenterology 131, 142-152.
5. Alvarez de la Rosa, D., Zhang, P., Shao, D., White, F. & Canessa, C.M. 2002. Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. Proc Natl Acad Sci USA 99, 2326-2331.
6. Banerjee, B., Medda, B.K., Lazarova, Z., Bansal, N., Shaker, R. & Sengupta, J.N. 2007. Effect of reflux-induced inflammation on transient receptor potential vanilloid one (TRPV1) expression in primary sensory neurons innervating the oesophagus of rats. Neurogastroenterol Motil 19, 681-691.
7. Bertrand, P.P., Kunze, W.A., Bornstein, J.C., Furness, J.B. & Smith, M.L. 1997. Analysis of the responses of myenteric neurons in the small intestine to chemical stimulation of the mucosa. Am J Physiol 273, G422-G435.
8. Bevan, S. & Geppetti, P. 1994. Protons: small stimulants of capsaicin-sensitive sensory nerves. Trends Neurosci 17, 509-512.
9. Bevan, S. & Yeats, J. 1991. Protons activate a cation conductance in a sub-population of rat dorsal root ganglion neurones. J Physiol 433, 145-161.
10. Bhat, Y.M. & Bielefeldt, K. 2006. Capsaicin receptor (TRPV1) and non-erosive reflux disease. Eur J Gastroenterol Hepatol 18, 263-270.
11. Bielefeldt, K. & Davis, B.M. 2008. Differential effects of ASIC3 and TRPV1 deletion on gastroesophageal sensation in mice. Am J Physiol 294, G130-G138.
12. Björne, H.H., Petersson, J., Phillipson, M., Weitzberg, E., Holm, L. & Lundberg, J.O. 2004. Nitrite in saliva increases gastric mucosal blood flow and mucus thickness. J Clin Invest 113, 106-114.
13. Burnstock, G. 2007. Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87, 659-797.
14. Caterina, M.J. & Julius, D. 2001. The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 24, 487-517.
15. Caterina, M.J., Leffler, A., Malmberg, A.B., Martin, W.J., Trafton, J., Petersen-Zeitz, K.R., Koltzenburg, M., Basbaum, A.I. & Julius, D. 2000. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288, 306-313.
16. Chan, C.L., Facer, P., Davis, J.B., Smith, G.D., Egerton, J., Bountra, C., Williams, N.S. & Anand, P. 2003. Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency. Lancet 361, 385-391.
17. Chen, C.C., Zimmer, A., Sun, W.H., Hall, J., Brownstein, M.J. & Zimmer, A. 2002. A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc Natl Acad Sci USA 99, 8992-8997.
18. Clapham, D.E., Julius, D., Montell, C. & Schultz, G. 2005. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol Rev 57, 427-450.
19. + channel. Am J Physiol 283, C1114-C1121.
20. Coffin, B., Chollet, R., Flourie, B., Lemann, M., Franchisseur, C., Rambaud, J.C. & Jian, R. 2001. Intraluminal modulation of gastric sensitivity to distension: effects of hydrochloric acid and meal. Am J Physiol 280, G904-G909.
21. Danzer, M., Jocic, M., Samberger, C., Painsipp, E., Bock, E., Pabst, M.A., Crailsheim, K., Schicho, R., Lippe, I.T. & Holzer, P. 2004. Stomach-brain communication by vagal afferents in response to luminal acid backdiffusion, gastrin, and gastric acid secretion. Am J Physiol 286, G403-G411.
22. Davis, J.B., Gray, J., Gunthorpe, M.J., Hatcher, J.P., Davey, P.T., Overend, P., Harries, M.H., Latcham, J., Clapham, C., Atkinson, K. et al. 2000. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405, 183-187.
23. Drewes, A.M., Schipper, K.P., Dimcevski, G., Petersen, P., Gregersen, H., Funch-Jensen, P. & Arendt-Nielsen, L. 2003. Gut pain and hyperalgesia induced by capsaicin: a human experimental model. Pain 104, 333-341.
24. Dunn, P.M., Zhong, Y. & Burnstock, G. 2001. P2X receptors in peripheral neurons. Prog Neurobiol 65, 107-134.
25. Duprat, F., Lauritzen, I., Patel, A. & Honoré, E. 2007. The TASK background K2P channels: chemo- and nutrient sensors. Trends Neurosci 30, 573-580.
26. Fallingborg, J. 1999. Intraluminal pH of the human gastrointestinal tract. Dan Med Bull 46, 183-196.
27. Forster, E.R., Green, T., Elliot, M., Bremner, A. & Dockray, G.J. 1990. Gastric emptying in rats: role of afferent neurons and cholecystokinin. Am J Physiol 258, G552-G556.
28. Fujino, K., De La Fuente, S.G., Takami, Y., Takahashi, T. & Mantyh, C.R. 2006. Attenuation of acid induced oesophagitis in VR-1 deficient mice. Gut 55, 34-40.
29. Geppetti, P., Tramontana, M., Evangelista, S., Renzi, D., Maggi, C.A., Fusco, B.M. & Del Bianco, E. 1991. Differential effect on neuropeptide release of different concentrations of hydrogen ions on afferent and intrinsic neurons of the rat stomach. Gastroenterology 101, 1505-1511.
30. Gerevich, Z., Zadori, Z.S., Köles, L., Kopp, L., Milius, D., Wirkner, K., Gyires, K. & Illes, P. 2007. Dual effect of acid pH on purinergic P2X3 receptors depends on the histidine 206 residue. J Biol Chem 282, 33949-33957.
31. Goldstein, S.A., Bayliss, D.A., Kim, D., Lesage, F., Plant, L.D. & Rajan, S. 2005. International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels. Pharmacol Rev 57, 527-540.
32. Hellwig, N., Plant, T.D., Janson, W., Schäfer, M., Schultz, G. & Schaefer, M. 2004. TRPV1 acts as proton channel to induce acidification in nociceptive neurons. J Biol Chem 279, 34553-34561.
33. Holm, M., Johansson, B., Pettersson, A. & Fändriks, L. 1998. Carbon dioxide mediates duodenal mucosal alkaline secretion in response to luminal acidity in the anesthetized rat. Gastroenterology 115, 680-685.
34. 2 and nitric oxide participate in the regulation of peptone-induced gastrin release in humans. Scand J Gastroenterol 35, 1260-1265.
35. Holzer, P. 1988. Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience 24, 739-768.
36. Holzer, P. 1991. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 43, 143-201.
37. Holzer, P. 1998. Neural emergency system in the stomach. Gastroenterology 114, 823-839.
38. Holzer, P. 2003. Acid-sensitive ion channels in gastrointestinal function. Curr Opin Pharmacol 3, 618-625.
39. Holzer, P. 2004. TRPV1 and the gut: from a tasty receptor for a painful vanilloid to a key player in hyperalgesia. Eur J Pharmacol 500, 231-241.
40. Holzer, P. 2007a. Taste receptors in the gastrointestinal tract. V. Acid sensing in the gastrointestinal tract. Am J Physiol 292, G699-G705.
41. Holzer, P. 2007b. Role of visceral afferent neurons in mucosal inflammation and defense. Curr Opin Pharmacol 7, 563-569.
42. Holzer, P. 2008. The pharmacological challenge to tame the transient receptor potential vanilloid-1 (TRPV1) nocisensor. Br J Pharmacol 155, 1145-1162.
43. Holzer, P. 2009. Acid-sensitive ion channels and receptors. Handb Exp Pharmacol 194, 283-332.
44. Holzer, P. & Maggi, C.A. 1998. Dissociation of dorsal root ganglion neurons into afferent and efferent-like neurons. Neuroscience 86, 389-398.
45. Holzer, P., Painsipp, E., Jocic, M. & Heinemann, A. 2003. Acid challenge delays gastric pressure adaptation, blocks gastric emptying and stimulates gastric fluid secretion in the rat. Neurogastroenterol Motil 15, 45-55.
46. Holzer, P., Wultsch, T., Edelsbrunner, M., Mitrovic, M., Shahbazian, A., Painsipp, E., Bock, E. & Pabst, M.A. 2007. Increase in gastric acid-induced afferent input to the brainstem in mice with gastritis. Neuroscience 145, 1108-1119.
47. 3 receptor antagonist, blocks acetic acid-induced abdominal constriction in mice: comparison with reference analgesics. Pain 96, 99-105.
48. Huang, J.Q. & Hunt, R.H. 1996. pH, healing rate and symptom relief in acid-related diseases. Yale J Biol Med 69, 159-174.
49. Huang, A.L., Chen, X., Hoon, M.A., Chandrashekar, J., Guo, W., Tränkner, D., Ryba, N.J. & Zuker, C.S. 2006. The cells and logic for mammalian sour taste detection. Nature 442, 934-938.
50. Huang, C.W., Tzeng, J.N., Chen, Y.J., Tsai, W.F., Chen, C.C. & Sun, W.H. 2007. Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors. Mol Cell Neurosci 36, 195-210.
51. Hughes, P.A., Brierley, S.M., Young, R.L. & Blackshaw, L.A. 2007. Localization and comparative analysis of acid-sensing ion channel (ASIC1, 2, and 3) mRNA expression in mouse colonic sensory neurons within thoracolumbar dorsal root ganglia. J Comp Neurol 500, 863-875.
52. Ikeda, Y., Ueno, A., Naraba, H. & Oh-ishi, S. 2001. Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice. Life Sci 69, 2911-2919.
53. Ishimaru, Y., Inada, H., Kubota, M., Zhuang, H., Tominaga, M. & Matsunami, H. 2006. Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci USA 103, 12569-12574.
54. Jancsó, N. 1960. Role of the nerve terminals in the mechanism of inflammatory reactions. Bull Millard Fillmore Hosp Buffalo 7, 53-77.
55. 2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proc Natl Acad Sci USA 99, 17179-17184.
56. Jiang, M., Dun, W. & Tseng, G.N. 1999. Mechanism for the effects of extracellular acidification on HERG-channel function. Am J Physiol 277, H1283-H1292.
57. Jordt, S.E., Tominaga, M. & Julius, D. 2000. Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc Natl Acad Sci USA 97, 8134-8139.
58. - response. Dig Dis Sci 48, 1850-1856.
59. Kang, J.Y. & Yap, I. 1991. Acid and gastric ulcer pain. J Clin Gastroenterol 13, 514-516.
60. Kellenberger, S. & Schild, L. 2002. Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure. Physiol Rev 82, 735-767.
61. Kress, M. & Waldmann, R. 2006. Acid sensing ionic channels. Curr Top Membranes 57, 241-276.
62. Krishtal, O.A. & Pidoplichko, V.I. 1981. A receptor for protons in the membrane of sensory neurons may participate in nociception. Neuroscience 6, 2599-2601.
63. Lamb, K., Kang, Y.M., Gebhart, G.F. & Bielefeldt, K. 2003. Gastric inflammation triggers hypersensitivity to acid in awake rats. Gastroenterology 125, 1410-1418.
64. Leffler, A., Mönter, B. & Koltzenburg, M. 2006. The role of the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) in proton sensitivity of subpopulations of primary nociceptive neurons in rats and mice. Neuroscience 139, 699-709.
65. LopezJimenez, N.D., Cavenagh, M.M., Sainz, E., Cruz-Ithier, M.A., Battey, J.F. & Sullivan, S.L. 2006. Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. J Neurochem 98, 68-77.
66. Lu, Y.X. & Owyang, C. 1999. Duodenal acid-induced gastric relaxation is mediated by multiple pathways. Am J Physiol 276, G1501-G1506.
67. Ludwig, M.G., Vanek, M., Guerini, D., Gasser, J.A., Jones, C.E., Junker, U., Hofstetter, H., Wolf, R.M. & Seuwen, K. 2003. Proton-sensing G-protein-coupled receptors. Nature 425, 93-98.
68. + exchanger-1 in rat taste receptor cells is involved in neural adaptation to acidic stimuli. J Physiol 556, 159-173.
69. Manela, F.D., Ren, J., Gao, J., McGuigan, J.E. & Harty, R.F. 1995. Calcitonin gene-related peptide modulates acid-mediated regulation of somatostatin and gastrin release from rat antrum. Gastroenterology 109, 701-706.
70. + (GIRK) channels by extracellular acidosis. J Biol Chem 277, 46166-46171.
71. Matthews, P.J., Aziz, Q., Facer, P., Davis, J.B., Thompson, D.G. & Anand, P. 2004. Increased capsaicin receptor TRPV1 nerve fibres in the inflamed human oesophagus. Eur J Gastroenterol Hepatol 16, 897-902.
72. Medda, B.K., Sengupta, J.N., Lang, I.M. & Shaker, R. 2005. Response properties of the brainstem neurons of the cat following intra-esophageal acid-pepsin infusion. Neuroscience 135, 1285-1294.
73. Miranda, A., Nordstrom, E., Mannem, A., Smith, C., Banerjee, B. & Sengupta, J.N. 2007. The role of transient receptor potential vanilloid 1 in mechanical and chemical visceral hyperalgesia following experimental colitis. Neuroscience 148, 1021-1032.
74. Mogil, J.S., Breese, N.M., Witty, M.F., Ritchie, J., Rainville, M.L., Ase, A., Abbadi, N., Stucky, C.L. & Seguela, P. 2005. Transgenic expression of a dominant-negative ASIC3 subunit leads to increased sensitivity to mechanical and inflammatory stimuli. J Neurosci 25, 9893-9901.
75. Montrose, M.H., Akiba, Y., Takeuchi, K. & Kaunitz, J.D. 2006. Gastroduodenal mucosal defense. In: L.R. Johnson (ed.) Physiology of the Gastrointestinal Tract, 4th edn, pp. 1259-1291. Academic Press, San Diego.
76. North, R.A. 2002. Molecular physiology of P2X receptors. Physiol Rev 82, 1013-1067.
77. Nugent, S.G., Kumar, D., Rampton, D.S. & Evans, D.F. 2001. Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs. Gut 48, 571-577.
78. Patapoutian, A., Peier, A.M., Story, G.M. & Viswanath, V. 2003. ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat Rev Neurosci 4, 529-539.
79. Patterson, L.M., Zheng, H., Ward, S.M. & Berthoud, H.R. 2003. Vanilloid receptor (VR1) expression in vagal afferent neurons innervating the gastrointestinal tract. Cell Tissue Res 311, 277-287.
80. Petersen, M. & LaMotte, R.H. 1993. Effect of protons on the inward current evoked by capsaicin in isolated dorsal root ganglion cells. Pain 54, 37-42.
81. Pohl, D., Fox, M., Fried, M., Göke, B., Prinz, C., Mönnikes, H., Rogler, G., Dauer, M., Keller, J., Lippl, F., Schiefke, I., Seidler, U., Allescher, H.D. & Kandahar Study Group. 2008. Do we need gastric acid? Digestion 77, 184-197.
82. Reeh, P.W. & Kress, M. 2001. Molecular physiology of proton transduction in nociceptors. Curr Opin Pharmacol 1, 45-51.
83. Rigoni, M., Trevisani, M., Gazzieri, D., Nadaletto, R., Tognetto, M., Creminon, C., Davis, J.B., Campi, B., Amadesi, S., Geppetti, P. & Harrison, S. 2003. Neurogenic responses mediated by vanilloid receptor-1 (TRPV1) are blocked by the high affinity antagonist, iodo-resiniferatoxin. Br J Pharmacol 138, 977-985.
84. Robinson, D.R., McNaughton, P.A., Evans, M.L. & Hicks, G.A. 2004. Characterization of the primary spinal afferent innervation of the mouse colon using retrograde labelling. Neurogastroenterol Motil 16, 113-124.
85. Rong, W., Hillsley, K., Davis, J.B., Hicks, G., Winchester, W.J. & Grundy, D. 2004. Jejunal afferent nerve sensitivity in wild-type and TRPV1 knockout mice. J Physiol 560, 867-881.
86. Ryu, S., Liu, B., Yao, J., Fu, Q. & Qin, F. 2007. Uncoupling proton activation of vanilloid receptor TRPV1. J Neurosci 27, 12797-12807.
87. Schicho, R., Schemann, M., Pabst, M.A., Holzer, P. & Lippe, I.T. 2003. Capsaicin-sensitive extrinsic afferents are involved in acid-induced activation of distinct myenteric neurons in the rat stomach. Neurogastroenterol Motil 15, 33-44.
88. Schicho, R., Florian, W., Liebmann, I., Holzer, P. & Lippe, I.T. 2004. Increased expression of TRPV1 receptor in dorsal root ganglia by acid insult of the rat gastric mucosa. Eur J Neurosci 19, 1811-1818.
89. Schmidt, B., Hammer, J., Holzer, P. & Hammer, H.F. 2004. Chemical nociception in the jejunum induced by capsaicin. Gut 53, 1109-1116.
90. Schuligoi, R., Jocic, M., Heinemann, A., Schöninkle, E., Pabst, M.A. & Holzer, P. 1998. Gastric acid-evoked c-fos messenger RNA expression in rat brainstem is signaled by capsaicin-resistant vagal afferents. Gastroenterology 115, 649-660.
91. Semtner, M., Schaefer, M., Pinkenburg, O. & Plant, T.D. 2007. Potentiation of TRPC5 by protons. J Biol Chem 282, 33868-33878.
92. Shulkes, A., Baldwin, G.S. & Giraud, A.S. 2006. Regulation of gastric acid secretion. In: L.R. Johnson (ed.) Physiology of the Gastrointestinal Tract, 4th edn, pp. 1223-1258. Academic Press, San Diego.
93. v1.3 inactivation: role of His399. Am J Physiol 287, C1067-C1076.
94. Steen, K.H., Reeh, P.W., Anton, F. & Handwerker, H.O. 1992. Protons selectively induce lasting excitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro. J Neurosci 12, 86-95.
95. Sugiura, T., Dang, K., Lamb, K., Bielefeldt, K. & Gebhart, G.F. 2005. Acid-sensing properties in rat gastric sensory neurons from normal and ulcerated stomach. J Neurosci 25, 2617-2627.
96. Sugiura, T., Bielefeldt, K. & Gebhart, G.F. 2007. Mouse colon sensory neurons detect extracellular acidosis via TRPV1. Am J Physiol 292, C1768-C1774.
97. Suzuki, M., Mizuno, A., Kodaira, K. & Imai, M. 2003. Impaired pressure sensation in mice lacking TRPV4. J Biol Chem 278, 22664-22668.
98. Szallasi, A. & Blumberg, P.M. 1999. Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 51, 159-212.
99. Szallasi, A., Cortright, D.N., Blum, C.A. & Eid, S.R. 2007. The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept. Nat Rev Drug Discov 6, 357-372.
100. Tang, L., Chen, Y., Chen, Z., Blumberg, P.M., Kozikowski, A.P. & Wang, Z.J. 2007. Antinociceptive pharmacology of N-(4-chlorobenzyl)-N'-(4-hydroxy-3-iodo-5-methoxybenzyl) thiourea, a high-affinity competitive antagonist of the transient receptor potential vanilloid 1 receptor. J Pharmacol Exp Ther 321, 791-798.
101. Tashima, K., Nakashima, M., Kagawa, S., Kato, S. & Takeuchi, K. 2002. Gastric hyperemic response induced by acid back-diffusion in rat stomachs following barrier disruption - relation to vanilloid type-1 receptors. Med Sci Monit 8, BR157-BR163.
102. Texter, E.C. 1987. Ulcer pain mechanisms. The clinical features of active peptic ulcer disease and implications for therapy. Scand J Gastroenterol Suppl 134, 1-20.
103. Tominaga, M., Caterina, M., Malmberg, A.B., Rosen, T.A., Gilbert, H., Skinner, K., Raumann, B.E., Basbaum, A.I. & Julius, D. 1998. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21, 531-543.
104. Tomura, H., Mogi, C., Sato, K. & Okajima, F. 2005. Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: a novel type of multi-functional receptors. Cell Signal 17, 1466-1476.
105. Urban, L., Campbell, E.A., Panesar, M., Patel, S., Chaudhry, N., Kane, S., Buchheit, K., Sandells, B. & James, I.F. 2000. In vivo pharmacology of SDZ 249-665, a novel, non-pungent capsaicin analogue. Pain 89, 65-74.
106. Vulcu, S.D., Liewald, J.F., Gillen, C., Rupp, J. & Nawrath, H. 2004. Proton conductance of human transient receptor potential-vanilloid type-1 expressed in oocytes of Xenopus laevis and in Chinese hamster ovary cells. Neuroscience 125, 861-866.
107. Wachter, C.H., Heinemann, A., Donnerer, J., Pabst, M.A. & Holzer, P. 1998. Mediation by 5-hydroxytryptamine of the femoral vasoconstriction induced by acid challenge of the rat gastric mucosa. J Physiol 509, 541-550.
108. Wemmie, J.A., Price, M.P. & Welsh, M.J. 2006. Acid-sensing ion channels: advances, questions and therapeutic opportunities. Trends Neurosci 29, 578-586.
109. Wultsch, T., Painsipp, E., Shahbazian, A., Mitrovic, M., Edelsbrunner, M., Waldmann, R., Lazdunski, M. & Holzer, P. 2008. Deletion of the acid-sensing ion channel ASIC3 prevents gastritis-induced acid hyperresponsiveness of the stomach-brainstem axis. Pain 134, 245-253.
110. Wynn, G., Ma, B., Ruan, H.Z. & Burnstock, G. 2004. Purinergic component of mechanosensory.transduction is increased in a rat model of colitis. Am J Physiol 287, G647-G657.
111. Xu, G.Y. & Huang, L.Y. 2002. Peripheral inflammation sensitizes P2X receptor-mediated responses in rat dorsal root ganglion neurons. J Neurosci 22, 93-102.
112. Xu, G.Y., Winston, J.H., Shenoy, M., Yin, H., Pendyala, S. & Pasricha, P.J. 2007. Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis. Gastroenterology 133, 1282-1292.
113. + channel δ subunit is an acid sensor in the human oesophagus. Eur J Pharmacol 600, 32-36.
114. 3 is increased in human inflammatory bowel disease. Neurogastroenterol Motil 13, 365-369.
115. Yiangou, Y., Facer, P., Dyer, N.H., Chan, C.L., Knowles, C., Williams, N.S. & Anand, P. 2001b. Vanilloid receptor 1 immunoreactivity in inflamed human bowel. Lancet 357, 1338-1339.
116. Yiangou, Y., Facer, P., Smith, J.A., Sangameswaran, L., Eglen, R., Birch, R., Knowles, C., Williams, N. & Anand, P. 2001c. Increased acid-sensing ion channel ASIC-3 in inflamed human intestine. Eur J Gastroenterol Hepatol 13, 891-896.
117. 2+ currents through capsaicin- and proton-activated ion channels in rat dorsal root ganglion neurones. J Physiol 503, 67-78.