Activation of G protein-coupled bile acid receptor, TGR5, induces smooth muscle relaxation via both Epac- and PKA-mediated inhibition of RhoA/Rho kinase pathway

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 304, Issue 5, 2013, Pages

  Rajagopal, Senthilkumar ^a   Kumar, Divya P ^a   Mahavadi, Sunila ^a   Bhattacharya, Sayak ^a   Zhou, Ruizhe ^a   Corvera, Carlos U ^b   Bunnett, Nigel W ^c   Grider, John R ^a   Murthy, Karnam S ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c MONASH UNIVERSITY   (Australia)

Author keywords

Bile acids; G protein coupled receptor; Oleanolic acid; Smooth muscle relaxation; TGR5 receptor

Indexed keywords

CARBACHOL; CYCLIC AMP; G PROTEIN COUPLED RECEPTOR; OLEANOLIC ACID; RAP1 PROTEIN; RHO KINASE; TGR5 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL STIMULATION; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; EXPERIMENTAL RABBIT; MOUSE; MUSCLE FIBER CONTRACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; SMOOTH MUSCLE RELAXATION; STOMACH MUSCLE; WESTERN BLOTTING;

ANIMALS; CELLS, CULTURED; CYCLIC AMP; CYCLIC AMP-DEPENDENT PROTEIN KINASES; GUANINE NUCLEOTIDE EXCHANGE FACTORS; MICE; MICE, KNOCKOUT; MUSCLE RELAXATION; MUSCLE, SMOOTH; OLEANOLIC ACID; PHOSPHORYLATION; POLYMERASE CHAIN REACTION; RABBITS; RECEPTORS, G-PROTEIN-COUPLED; RHO-ASSOCIATED KINASES; RHOA GTP-BINDING PROTEIN; RNA, SMALL INTERFERING; TRANSFECTION;

EID: 84874630085     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00388.2012     Document Type: Article

References (38)

1. Bala V, Mahavadi S, Rajagopal S, Zhou R, Kuemmerle FJ, Sanyal JA, Murthy KS. Bile acid-induced stimulation of ERK1/2 activity, GLP-1 and PYY release in enteroendocrine cells are mediated by the activation of Epac/PLC-EEsignaling pathway via GS-coupled TGR5. Gastroenterology 140: S147, 2011.
2. Breckler M, Berthouze M, Laurent AC, Crozatier B, Morel E, Lezoualc'h F. Rap-linked cAMP signaling Epac proteins: compartmentation, functioning and disease implications. Cell Signal 23: 1257-1266, 2011.
3. Cullere X, Shaw SK, Anderson K, Hirahashi J, Luscinskas FW, Mayadas TN. Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase. Blood 105: 1950-1955, 2005.
4. Emmanuelle C. Cellular functions of the Rap1 GTP-binding protein: a pattern emerges. J Cell Sci 116: 435-440, 2003.
5. Fiorucci S, Cipriani S, Mencarelli A, Renga B, Distrutti E, Baldelli F. Counter regulatory role of bile acid activated receptors in immunity and inflammation. Curr Mol Med 10: 579-595, 2010.
6. Houten S, Watanabe M, Auwerx J. Endocrine functions of bile acids. EMBO J 25: 1419-1425, 2006.
7. 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 329: 386-390, 2005.
8. Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, Miwa M, Fukusumi S, Habata Y, Itoh T, Shintani Y, Hinuma S, Fujisawa Y, Fujino M. A G protein-coupled receptor responsive to bile acids. J Biol Chem 278: 9435-9440, 2003.
9. 2+ sensitization in rabbit smooth muscle. J Physiol 546: 879-889, 2003.
10. Knop FK. Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes? Am J Physiol Endocrinol Metab 299: E10-E13, 2010.
11. Lavoie B, Balemba OB, Godfrey C, Watson CA, Vassileva G, Corvera CU, Nelson MT, Mawe G. Hydrophobic bile salts inhibit gallbladder smooth muscle function via stimulation of GPBAR1 reporters and activation of KATP channels. J Physiol 588: 3295-3305, 2010.
12. Li T, Holmstrom SR, Kir S, Umetani M, Schimidt DR, Kliewer SA, Mangelsdorf DJ. The G protein-coupled bile acid receptor, TGR5 stimulates gallbladder filling. Mol Endocrinol 25: 1066-1071, 2011.
13. Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, Mangelsdorf DJ. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell Biol 6: 507-515, 2000.
14. Ma K, Saha P, Chan L, Moore DD. Farnesoid X receptor is essential for normal glucose homestasis. J Clin Invest 116: 1102-1109, 2006.
15. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Manglesdorf DJ, Shan B. Identification of nuclear receptors for bile acids. Science 284: 1362-1365, 1999.
16. Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, Sugiyama E, Nakamura T, Itadani H, Tanaka K. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun 298: 714-719, 2002.
17. Murthy KS. Signaling for contraction and relaxation in smooth muscle of the gut. Annu Rev Physiol 68: 345-374, 2006.
18. Murthy KS, Jin JG, Grider JR, Makhlouf GM. Characterization of PACAP receptors and signaling pathways in rabbit gastric smooth muscle cells. Am J Physiol Gastrointest Liver Physiol 272: G1391-G1399, 1997.
19. Murthy KS, Makhlouf GM. Differential coupling of muscarinic m2 and m3 receptors to adenylyl cyclases V/VI in smooth muscle. J Biol Chem 272: 21317-21324, 1997.
20. Murthy KS, Zhou H, Grider JR, Brautigan D, Eto M, Makhlouf GM. Differential signaling by muscarinic receptors in smooth muscle: m2 mediated inactivation of myosin light chain kinase via Gi3, cdc42/Rac1 and p21-activated kinase pathway, and m3-mediated MLC20 phosphorylation via Rho-associated kinase/myosin phosphatase targeting subunit I and protein kinase C/CPI 17 pathway. Biochem J 374: 145-155, 2003.
21. Murthy KS, Zhou H, Grider JR, Makhlouf GM. Inhibition of sustained smooth muscle contraction by PKA and PKG preferentially mediated by phosphorylation of RhoA. Am J Physiol Gastrointest Liver Physiol 284: G1006-G1016, 2003.
22. Okamoto T, Murayama Y, Hayashi Y, Inagaki M, Ogata E, Nishimoto I. Identification of a Gs activator region of the β2-adrenergic receptor that is autoregulated via protein kinase A-dependent phosphorylation. Cell 67: 723-730, 1991.
23. Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Morre DD, Lehmann JM. Bile acids: Natural ligands for an orphan nuclear receptor. Science 284: 1365-1368, 1999.
24. Paul A, Tian L, Rao A. Bile acid transporters. J Lipid Res 50: 2340-2357, 2009.
25. Poole DP, Godfrey C, Cattaruzza F, Cottrell GS, Kirkland JG, Pelayo JC, Bunnett NW, Corvera CU. Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system. Neurogastroenterol Motil 22: 814-825, 2010.
26. Roscioni SS, Maarsingh H, Elzinga CR, Schuur J, Menzen M, Halayko AJ, Meurs H, Schmidt M. Epac as a novel effector of airway smooth muscle relaxation. J Cell Mol Med 15: 1551-1563, 2011.
27. Sato H, Genet C, Strehle A, Thomas C, Lobstein A, Wagner A, Mioskowski C, Auwerx J, Saladin R. Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea. Biochem Biophys Res Commun 362: 793-798, 2007.
28. 2+ sensitization of contraction in vascular smooth muscle. J Biol Chem 275: 21722-21729, 2000.
29. Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102: 731-744, 2000.
30. 2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83: 1325-1358, 2003.
31. Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, Macchiarulo A, Yamamoto H, Mataki C, Pruzanski M, Pellicciari R, Auwerx J, Schoonjans K. TGR5-mediated bile acid sensing controls glucose homestasis. Cell Metabol 10: 167-177, 2009.
32. Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K. Targeting bile-acid signaling for metabolic diseases. Nat Rev Drug Dis 7: 678-693, 2008.
33. Vassileva G, Golovko A, Markowitz L, Abbondanzo SJ, Zeng M, Yang S, Hoos L, Tetzloff G, Levitan D, Murgolo NJ, Keane K, Davis HJ, Hedrick J, Gustafson EL. Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation. Biochem J 398: 423-430, 2006.
34. Wang H, Chen J, Hollister K, Sowers LC, Forman BM. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell Biol 3: 543-553, 1999.
35. Yamada T, Sakisaka T, Hisata S, Baba T, Takai Y. RA-RhoGAP, Rap-activated Rho GTPase-activating protein implicated in neurite outgrowth through Rho. J Biol Chem 280: 33026-33034, 2005.
36. Yanqiao Z, Florence Y, Gabriel B, Hans L, Charisse V, Frank JG, Timothy MW, Peter AE. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci USA 103: 1006-1011, 2006.
37. Yokoyama U, Patel HH, Lai NC, Aroonsakool N, Roth DM, Insel PA. The cyclic AMP effector Epac integrates pro-and anti-fibrotic signals. Proc Natl Acad Sci USA 105: 6386-6391, 2008.
38. Zieba BJ, Artamonov MV, Jin L, Momotani K, Ho R, Franke AS, Neppl RL, Stevenson AS, Khromov AS, Wodnicka MC, Somlyo AV. The cAMP-responsive Rap1 guanine nucleotide exchange factor, Epac, induces smooth muscle relaxation by down-regulation of RhoA activity. J Biol Chem 286: 16681-16692, 2011.