The TGR5 receptor mediates bile acid-induced itch and analgesia

Journal of Clinical Investigation

Volumn 123, Issue 4, 2013, Pages 1513-1530

  Alemi, Farzad ^a   Kwon, Edwin ^a   Poole, Daniel P ^b   Lieu, TinaMarie ^c   Lyo, Victoria ^a   Cattaruzza, Fiore ^a   Cevikbas, Ferda ^a   Steinhoff, Martin ^a   Nassini, Romina ^d   Materazzi, Serena ^d   Guerrero Alba, Raquel ^e   Valdez Morales, Eduardo ^e   Cottrell, Graeme S ^f   Schoonjans, Kristina ^g   Geppetti, Pierangelo ^d   Vanner, Stephen J ^e   Bunnett, Nigel W ^c   Corvera, Carlos U ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c MONASH UNIVERSITY   (Australia)

^d UNIVERSITY OF FLORENCE   (Italy)

^e QUEEN S UNIVERSITY   (Canada)

^f University of Bath   (United Kingdom)

^g Chemical Engineering and Biochemistry Section   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BILE ACID; G PROTEIN COUPLED RECEPTOR; GASTRIN RELEASING PEPTIDE; LEUCINE ENKEPHALIN; NEUROPEPTIDE; OPIATE AGONIST; TGR5 RECEPTOR; UNCLASSIFIED DRUG;

ANALGESIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHOLESTASIS; CONTROLLED STUDY; DISEASE EXACERBATION; FEMALE; JAUNDICE; MALE; MECHANICAL STIMULATION; MOUSE; NERVE CELL; NERVE CELL EXCITABILITY; NEUROTRANSMITTER RELEASE; NONHUMAN; PEPTIDERGIC NERVOUS SYSTEM; PRIORITY JOURNAL; PRURITUS; SCRATCHING; SENSORY NERVE; SPINAL CORD; SPINAL GANGLION;

ACTION POTENTIALS; ANIMALS; BILE ACIDS AND SALTS; CAPSAICIN; CELLS, CULTURED; CHOLESTASIS; DERMIS; ENKEPHALIN, LEUCINE; FEMALE; GANGLIA, SPINAL; GASTRIN-RELEASING PEPTIDE; GENE EXPRESSION; MACROPHAGES; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NEURONS; OPIOID PEPTIDES; ORGAN SPECIFICITY; PAIN; PAIN PERCEPTION; PATCH-CLAMP TECHNIQUES; PRURITUS; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, G-PROTEIN-COUPLED; SINGLE-CELL ANALYSIS; SPINAL CORD;

EID: 84875848761     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI64551     Document Type: Article

References (68)

1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of cholestatic liver diseases. J Hepatol. 2009;51(2):237-267.
2. Bergasa NV. The itch of liver disease. Semin Cutan Med Surg. 2011;30(2):93-98.
3. Fitzgerald JE, White MJ, Lobo DN. Courvoisier's gallbladder: Law or sign? World J Surg. 2009;33(4):886-891.
4. Moretti EW, Robertson KM, Tuttle-Newhall JE, Clavien PA, Gan TJ. Orthotopic liver transplant patients require less postoperative morphine than do patients undergoing hepatic resection. J Clin Anesth. 2002;14(6):416-420.
5. Nelson L, Vergnolle N, D'Mello C, Chapman K, Le T, Swain MG. Endogenous opioid-mediated antinociception in cholestatic mice is peripherally, not centrally, mediated. J Hepatol. 2006;44(6):1141-1149.
6. Patel KN, Dong X. An itch to be scratched. Neuron. 2010;68(3):334-339.
7. Ward L, Wright E, McMahon SB. A comparison of the effects of noxious and innocuous counterstimuli on experimentally induced itch and pain. Pain. 1996;64(1):129-138.
8. Slappendel R, Weber EW, Benraad B, van Limbeek J, Dirksen R. Itching after intrathecal morphine. Incidence and treatment. Eur J Anaesthesiol. 2000;17(10):616-621.
9. Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjork HE. Specific C-receptors for itch in human skin. J Neurosci. 1997;17(20):8003-8008.
10. Sun YG, Chen ZF. A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature. 2007;448(7154):700-703.
11. Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY, Chen ZF. Cellular basis of itch sensation. Science. 2009; 325(5947):1531-1534.
12. Liu XY, et al. Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids. Cell. 2011;147(2):447-458.
13. Schmelz M, Schmidt R, Weidner C, Hilliges M, Torebjork HE, Handwerker HO. Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens. J Neurophysiol. 2003; 89(5):2441-2448.
14. Imamachi N, et al. TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms. Proc Nat Acad Sci. 2009;106(27):11330-11335.
15. Lagerstrom MC, et al. VGLUT2-dependent sensory neurons in the TRPV1 population regulate pain and itch. Neuron. 2010;68(3):529-542.
16. Liu Y, et al. VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch. Neuron. 2010;68(3):543-556.
17. McMahon SB, Koltzenburg M. Itching for an explanation. Trends Neurosci. 1992;15(12):497-501.
18. Magyar I, Loi HG, Feher T. Plasma bile acid levels and liver disease. Acta Med Acad Sci Hung. 1981; 38(2):109-115.
19. Schoenfield LJ, Sjorvall J, Perman E. Bile acids on the skin of patients with pruritic hepatobiliary disease. Nature. 1967;213:93-94.
20. Kirby J, Heaton KW, Burton JL. Pruritic effect of bile salts. Br Med J. 1974;4(5946):693-695.
21. Varadi DP. Pruritus induced by crude bile and purified bile acids. Experimental production of pruritus in human skin. Arch Dermatol. 1974;109(5):678-681.
22. Mela M, Mancuso A, Burroughs AK. Review article: Pruritus in cholestatic and other liver diseases. Aliment Pharmacol Ther. 2003;17(7):857-870.
23. Thornton JR, Losowsky MS. Plasma leucine enkephalin is increased in liver disease. Gut. 1989; 30(10):1392-1395.
24. Swain MG, Rothman RB, Xu H, Vergalla J, Bergasa NV, Jones EA. Endogenous opioids accumulate in plasma in a rat model of acute cholestasis. Gastroenterology. 1992;103(2):630-635.
25. Bergasa NV, Rothman RB, Vergalla J, Xu H, Swain MG, Jones EA. Central mu-opioid receptors are down-regulated in a rat model of cholestasis. J Hepatol. 1992;15(1-2):220-224.
26. Bergasa NV, et al. A controlled trial of naloxone infusions for the pruritus of chronic cholestasis. Gastroenterology. 1992;102(2):544-549.
27. Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K. Targeting bile-acid signalling for metabolic diseases. Nat Rev Drug Discov. 2008; 7(8):678-693.
28. Kawamata Y, et al. A G protein-coupled receptor responsive to bile acids. J Biol Chem. 2003; 278(11):9435-9440.
29. Maruyama T, et al. Identification of membranetype receptor for bile acids (M-BAR). Biochem Biophys Res Commun. 2002;298(5):714-719.
30. Watanabe M, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484-489.
31. Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005;329(1):386-390.
32. Thomas C, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009; 10(3):167-177.
33. Keitel V, Cupisti K, Ullmer C, Knoefel WT, Kubitz R, Haussinger D. The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders. Hepatology. 2009;50(3):861-870.
34. Lavoie B, et al. Hydrophobic bile salts inhibit gallbladder smooth muscle function via stimulation of GPBAR1 receptors and activation of KATP channels. J Physiol. 2010;588(pt 17):3295-3305.
35. Li T, et al. The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling. Mol Endocrinol. 2011;25(6):1066-1071.
36. Maruyama T, et al. Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice. J Endocrinol. 2006;191(1):197-205.
37. Pols TW, et al. TGR5 Activation Inhibits Atherosclerosis by Reducing Macrophage Inflammation and Lipid Loading. Cell Metab. 2011;14(6):747-757.
38. Wang YD, Chen WD, Yu D, Forman BM, Huang W. The G-Protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor kappa light-chain enhancer of activated B cells (NFkappaB) in mice. Hepatology. 2011;54(4):1421-1432.
39. Poole DP, et al. Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system. Neurogastroenterol Motil. 2010;22(7):814-825, e227-818.
40. Keitel V, et al. The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain. Glia. 2010;58(15):1794-1805.
41. Sato H, et al. Novel potent and selective bile acid derivatives as TGR5 agonists: Biological screening, structure-activity relationships, and molecular modeling studies. J Med Chem. 2008;51(6):1831-1841.
42. Liu T, et al. TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice. J Clin Invest. 2012;122(6):2195- 2207.
43. Shim WS, et al. TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase. J Neurosci. 2007;27(9):2331-2337.
44. Wilson SR, et al. TRPA1 is required for histamineindependent, Mas-related G protein-coupled receptor-mediated itch. Nat Neurosci. 2011;14(5):595-602.
45. Bunnett NW, et al. Canine bombesin-like gastrin releasing peptides stimulate gastrin release and acid secretion in the dog. J Physiol. 1985;365:121-130.
46. Labuz D, et al. Peripheral antinociceptive effects of exogenous and immune cell-derived endomorphins in prolonged inflammatory pain. J Neurosci. 2006;26(16):4350-4358.
47. Kayssi A, Amadesi S, Bautista F, Bunnett NW, Vanner S. Mechanisms of protease-activated receptor 2-evoked hyperexcitability of nociceptive neurons innervating the mouse colon. J Physiol. 2007; 580(pt 3):977-991.
48. Sato H, et al. Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea. Biochem Biophys Res Commun. 2007;362(4):793-798.
49. Iguchi Y, Nishimaki-Mogami T, Yamaguchi M, Teraoka F, Kaneko T, Une M. Effects of chemical modification of ursodeoxycholic acid on TGR5 activation. Biol Pharm Bull. 2011;34(1):1-7.
50. Fleming MS, Ramos D, Han SB, Zhao J, Son YJ, Luo W. The majority of dorsal spinal cord gastrin releasing peptide is synthesized locally whereas neuromedin B is highly expressed in pain-and itch-sensing somatosensory neurons. Mol Pain. 2012;8(1):52.
51. Glazer EJ, Basbaum AI. Immunohistochemical localization of leucine-enkephalin in the spinal cord of the cat: Enkephalin-containing marginal neurons and pain modulation. J Comp Neurol. 1981; 196(3):377-389.
52. Weidner C, et al. Acute effects of substance P and calcitonin gene-related peptide in human skin-a microdialysis study. J Invest Dermatol. 2000; 115(6):1015-1020.
53. Heinz-Erian P, Coy DH, Tamura M, Jones SW, Gardner JD, Jensen RT. [D-Phe12]bombesin analogues: A new class of bombesin receptor antagonists. Am J Physiol. 1987;252(3 pt 1):G439-G442.
54. Ko MC, Naughton NN. An experimental itch model in monkeys: Characterization of intrathecal morphine-induced scratching and antinociception. Anesthesiology. 2000;92(3):795-805.
55. Hashimoto T, Ohata H, Momose K. Itch-scratch responses induced by lysophosphatidic acid in mice. Pharmacol. 2004;72(1):51-56.
56. Kremer AE, et al. Lysophosphatidic acid is a potential mediator of cholestatic pruritus. Gastroenterology. 2010;139(3):1008-1018.
57. Koga K, et al. Glutamate acts as a neurotransmitter for gastrin releasing peptide-sensitive and insensitive itch-related synaptic transmission in mammalian spinal cord. Mol Pain. 2011;7:47.
58. Angelin B, Bjorkhem I, Einarsson K, Ewerth S. Hepatic uptake of bile acids in man. Fasting and postprandial concentrations of individual bile acids in portal venous and systemic blood serum. J Clin Invest. 1982;70(4):724-731.
59. Mano N, et al. Presence of protein-bound unconjugated bile acids in the cytoplasmic fraction of rat brain. J Lipid Res. 2004;45(2):295-300.
60. Ogundare M, et al. Cerebrospinal fluid steroidomics: Are bioactive bile acids present in brain? J Biol Chem. 2010;285(7):4666-4679.
61. Bron B, Waldram R, Silk DB, Williams R. Serum, cerebrospinal fluid, and brain levels of bile acids in patients with fulminant hepatic failure. Gut. 1977;18(9):692-696.
62. Bartholomew TC, Summerfield JA, Billing BH, Lawson AM, Setchell KD. Bile acid profiles of human serum and skin interstitial fluid and their relationship to pruritus studied by gas chromatographymass spectrometry. Clin Sci. 1982;63(1):65-73.
63. Lieu T, Undem BJ. Neuroplasticity in vagal afferent neurons involved in cough. Pul Pharm Ther. 2011;24(3):276-279.
64. Gibbins IL, Furness JB, Costa M, MacIntyre I, Hillyard CJ, Girgis S. Co-localization of calcitonin gene-related peptide-like immunoreactivity with substance P in cutaneous, vascular and visceral sensory neurons of guinea pigs. Neurosci Lett. 1985; 57(2):125-130.
65. Cuello AC, Galfre G, Milstein C. Detection of substance P in the central nervous system by a monoclonal antibody. Proc Nat Acad Sci. 1979;76(7):3532- 3536.
66. Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurol. 1998;50(3):652-657.
67. Amadesi S, et al. Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. J Neurosci.2004;24(18):4300-4312.
68. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Meth. 1994;53(1):55-63.