The multiple roles of guanylate cyclase C, a heat stable enterotoxin receptor

Current Opinion in Gastroenterology

Volumn 30, Issue 1, 2014, Pages 1-6

  Steinbrecher, Kris A ^a  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

Author keywords

cGMP; guanylate cyclase; infection; inflammatory bowel disease; irritable bowel syndrome

Indexed keywords

CYCLIC GMP; ENTEROTOXIN; GUANYLATE CYCLASE; GUANYLATE CYCLASE C; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; BACTERIAL INFECTION; BACTERIAL LOAD; CITROBACTER RODENTIUM; COLITIS; COLON INJURY; CONSTIPATION; CYSTIC FIBROSIS; DEHYDRATION; DIARRHEA; DIGESTIVE SYSTEM INFLAMMATION; DISEASE PREDISPOSITION; ENTERITIS; ENTEROPATHY; ESCHERICHIA COLI; FLUID BALANCE; GASTROINTESTINAL DISEASE; GENE MUTATION; HUMAN; INTESTINE; INTESTINE FLORA; INTESTINE INFECTION; INTESTINE OBSTRUCTION; IRRITABLE COLON; MECONIUM ILEUS; NONHUMAN; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; VISCERAL PAIN; WATER FLOW;

ADHESINS, BACTERIAL; HOMEOSTASIS; HUMANS; INFLAMMATORY BOWEL DISEASES; INTESTINAL ABSORPTION; INTESTINES; IRRITABLE BOWEL SYNDROME; RECEPTORS, ATRIAL NATRIURETIC FACTOR; SIGNAL TRANSDUCTION; WATER-ELECTROLYTE BALANCE;

EID: 84890333028     PISSN: 02671379     EISSN: 15317056     Source Type: Journal    
DOI: 10.1097/MOG.0000000000000020     Document Type: Review

References (58)

1. Taxt A, Aasland R, Sommerfelt H, et al. Heat-stable enterotoxin of enterotoxigenic Escherichia coli as a vaccine target. Infect Immun2010; 78:1824-1831.
2. WHO. Future directions for research on enterotoxigenic Escherichia coli vaccines for developing countries. Wkly Epidemiol Rec 2006; 81:97-104.
3. Field M, Graf LH Jr, Laird WJ, Smith PL. Heat-stable enterotoxin of Escherichia coli: In vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc Natl Acad Sci U S A 1978; 75:2800-2804.
4. Hughes JM, Murad F, Chang B, Guerrant RL. Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli. Nature 1978; 271:755-756.
5. Mezoff AG, Jensen NJ, Cohen MB. Mechanisms of increased susceptibility of immature and weaned pigs to Escherichia coli heat-stable enterotoxin. Pediatr Res 1991; 29:424-428.
6. Cohen MB, Moyer MS, Luttrell M, Giannella RA. The immature rat small intestine exhibits an increased sensitivity and response to Escherichia coli heat-stable enterotoxin. Pediatr Res 1986; 20:555-560.
7. Guarino A, Cohen MB, Giannella RA. Small and large intestinal guanylate cyclase activity in children: Effect of age and stimulation by Escherichia coli heat-stable enterotoxin. Pediatr Res 1987; 21:551-555.
8. Cohen MB, Guarino A, Shukla R, Giannella RA. Age-related differences in receptors for Escherichia coli heat-stable enterotoxin in the small and large intestine of children. Gastroenterology 1988; 94:367-373.
9. Schulz S, Green CK, Yuen PS, Garbers DL. Guanylyl cyclase is a heat-stable enterotoxin receptor. Cell 1990; 63:941-948.
10. Arshad N, Ballal S, Visweswariah SS. Site-specific N-linked glycosylation of receptor guanylyl cyclase C regulates ligand binding, ligand-mediated activation and interaction with vesicular integral membrane protein 36, VIP36. J Biol Chem 2013; 288:3907-3917.
11. Zuzga DS, Pelta-Heller J, Li P, et al. Phosphorylation of vasodilator-stimulated phosphoprotein Ser239 suppresses filopodia and invadopodia in colon cancer. Int J Cancer 2012; 130:2539-2548.
12. Lan T, Chen Y, Sang J, et al. Type II cGMP-dependent protein kinase inhibits EGF-induced MAPK/JNK signal transduction in breast cancer cells. Oncol Rep 2012; 27:2039-2044.
13. Sang J, Chen Y, Jiang L, et al. Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells. Mol Med Rep 2012; 6:1190-1194.
14. Wang R, Kwon IK, Thangaraju M, et al. Type 2 cGMP-dependent protein kinase regulates proliferation and differentiation in the colonic mucosa. Am J Physiol Gastrointest Liver Physiol 2012; 303:G209-219.
15. Gong R, Ding C, Hu J, et al. Role for the membrane receptor guanylyl cyclase-C in attention deficiency and hyperactive behavior. Science 2011; 333:1642-1646.
16. Valentino MA, Lin JE, Snook AE, et al. A uroguanylin-GUCY2C endocrine axis regulates feeding in mice. J Clin Invest 2011; 121:3578-3588.
17. Moss NG, Fellner RC, Qian X, et al. Uroguanylin, an intestinal natriuretic peptide, is delivered to the kidney as an unprocessed propeptide. Endocrinology 2008; 149:4486-4498.
18. Brierley SM. Guanylate cyclase-C receptor activation: Unexpected biology. Curr Opin Pharmacol 2012; 12:632-640.
19. Tal A, Carmi R, Chai-Am E, et al. Familial meconium ileus with normal sweat electrolytes. Clin Pediatr (Phila) 1985; 24:460-462.
20. Romi H, Cohen I, Landau D, et al. Meconium ileus caused by mutations in GUCY2C, encoding the CFTR-activating guanylate cyclase 2C. Am J Hum Genet 2012; 90:893-899. This manuscript describes familial inheritance of loss-of-function GC-C mutations that cause noncystic fibrosis meconium ileus and highlights the critical function of GC-C during the neonatal period.
21. Fiskerstrand T, Arshad N, Haukanes BI, et al. Familial diarrhea syndrome caused by an activating GUCY2C mutation. N Engl J Med 2012; 366:1586-1595. This article describes familial inheritance of gain-of-function GC-C mutations that cause chronic diarrhea, obstruction and increased susceptibility to IBD.
22. Sun L, Rommens JM, Corvol H, et al. Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis. Nat Genet 2012; 44:562-569.
23. Mann EA, Harmel-Laws E, Cohen MB, Steinbrecher KA. Guanylate cyclase C limits systemic dissemination of a murine enteric pathogen. BMC Gastroenterol 2013; 13:135. Although GC-C is a target for the bacterial enterotoxin STa, this article demonstrates that GC-C regulates commensal microflora and reduces susceptibility to infection by attaching/effacing bacterial pathogens.
24. Bergstrom KS, Sham HP, Zarepour M, Vallance BA. Innate host responses to enteric bacterial pathogens: A balancing act between resistance and tolerance. Cell Microbiol 2012; 14:475-484.
25. Garcia MA, Yang N, Quinton PM. Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion. J Clin Invest 2009; 119:2613-2622.
26. Snouwaert JN, Brigman KK, Latour AM, et al. An animal model for cystic fibrosis made by gene targeting. Science 1992; 257:1083-1088.
27. Norkina O, Kaur S, Ziemer D, De Lisle RC. Inflammation of the cystic fibrosis mouse small intestine. Am J Physiol Gastrointest Liver Physiol 2004; 286:G1032-G1041.
28. Laubitz D, Larmonier CB, Bai A, et al. Colonic gene expression profile in NHE3-deficient mice: Evidence for spontaneous distal colitis. Am J Physiol Gastrointest Liver Physiol 2008; 295:G63-G77.
29. Stecher B, Chaffron S, Kappeli R, et al. Like will to like: Abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria. PLoS Pathog 2010; 6:e1000711.
30. Busby RW, Bryant AP, Bartolini WP, et al. Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur J Pharmacol 2010; 649:328-335.
31. Johnston JM, Kurtz CB, Macdougall JE, et al. Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation. Gastroenterology 2010; 139:1877-1886.
32. Shailubhai K, Comiskey S, Foss JA, et al. Plecanatide, an oral guanylate cyclase C agonist acting locally in the gastrointestinal tract, is safe and well tolerated in single doses. Dig Dis Sci 2013; 58:2580-2586.
33. Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: A 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol 2012; 107:1702-1712.
34. Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol 2012; 107:1714-1724. Along with references [32] and [33], this report describes recent progress in the clinical development of therapeutic GC-C peptide agonists.
35. Silos-Santiago I, Hannig G, Eutamene H, et al. Gastrointestinal pain: Unraveling a novel endogenous pathway through uroguanylin/guanylate cyclase-C/cGMP activation. Pain 2013; 154:1820-1830.
36. Castro J, Harrington AM, Hughes PA, et al. Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic GMP. Gastroenterology 2013. [Epub ahead of print] Along with reference [35], these reports present evidence of a novel GC-Cdependent signaling pathway that utilizes basolateral release of cGMP from epithelial cells to signal to enteric neurons.
37. Feng B, Kiyatkin ME, La JH, et al. Activation of guanylate cyclase-C attenuates stretch responses and sensitization of mouse colorectal afferents. J Neurosci 2013; 33:9831-9839.
38. Blackshaw LA, Brierley SM. Emerging receptor target in the pharmacotherapy of irritable bowel syndrome with constipation. Expert Rev Gastroenterol Hepatol 2013; 7:15-19.
39. Steinbrecher KA, Harmel-Laws E, Garin-Laflam MP, et al. Murine guanylate cyclase C regulates colonic injury and inflammation. J Immunol 2011; 186:7205-7214.
40. Hogan SP, Seidu L, Blanchard C, et al. Resistin-like molecule beta regulates innate colonic function: Barrier integrity and inflammation susceptibility. J Allergy Clin Immunol 2006; 118:257-268.
41. McVay LD, Keilbaugh SA, Wong TM, et al. Absence of bacterially induced RELMbeta reduces injury in the dextran sodium sulfate model of colitis. J Clin Invest 2006; 116:2914-2923.
42. Lin JE, Snook AE, Li P, et al. GUCY2C opposes systemic genotoxic tumorigenesis by regulating AKT-dependent intestinal barrier integrity. PLoS One 2012; 7:e31686.
43. Itoh H, Beck PL, Inoue N, et al. A paradoxical reduction in susceptibility to colonic injury upon targeted transgenic ablation of goblet cells. J Clin Invest 1999; 104:1539-1547.
44. Cuppoletti J, Blikslager AT, Chakrabarti J, et al. Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors. BMC Pharmacol 2012; 12:3.
45. Nakashima R, Kamata Y, Nishikawa Y. Effects of Escherichia coli heat-stable enterotoxin and guanylin on the barrier integrity of intestinal epithelial T84 cells. Vet Immunol Immunopathol 2013; 152:78-81.
46. Han X, Mann E, Gilbert S, et al. Loss of guanylyl cyclase C.(GCC) signaling leads to dysfunctional intestinal barrier. PLoS One 2011; 6:e16139.
47. Ubeda C, Lipuma L, Gobourne A, et al. Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice. J Exp Med 2012; 209:1445-1456.
48. Vijay-Kumar M, Aitken JD, Carvalho FA, et al. Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor
49. Vijay-Kumar M, Sanders CJ, Taylor RT, et al. Deletion of TLR5 results in spontaneous colitis in mice. J Clin Invest 2007; 117:3909-3921.
50. Berg DJ, Davidson N, Kuhn R, et al. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4() TH1-like responses. J Clin Invest 1996; 98:1010-1020.
51. Paul G, Khare V, Gasche C. Inflamed gut mucosa: Downstream of interleukin- Eur J Clin Invest 2012; 42:95-109.
52. Wu F, Dassopoulos T, Cope L, et al. Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: Insights into distinctive pathogenesis. Inflamm Bowel Dis 2007; 13:807-821.
53. De Lisle RC, Mueller R, Boyd M. Impaired mucosal barrier function in the small intestine of the cystic fibrosis mouse. J Pediatr Gastroenterol Nutr 2011; 53:371-379.
54. Norkina O, Burnett TG, De Lisle RC. Bacterial overgrowth in the cystic fibrosis transmembrane conductance regulator null mouse small intestine. Infect Immun 2004; 72:6040-6049.
55. Kiela PR, Laubitz D, Larmonier CB, et al. Changes in mucosal homeostasis predispose NHE3 knockout mice to increased susceptibility to DSS-induced epithelial injury. Gastroenterology 2009; 137:965-975.
56. Larmonier CB, Laubitz D, Thurston RD, et al. NHE3 modulates the severity of colitis in IL-10-deficient mice. Am J Physiol Gastrointest Liver Physiol 2011; 300:G998-G1009.
57. Wehkamp J, Salzman NH, Porter E, et al. Reduced Paneth cell alphadefensins in ileal Crohn's disease. Proc Natl Acad Sci U S A 2005; 102:18129-18134.
58. Wehkamp J, Schmid M, Stange EF. Defensins and other antimicrobial peptides in inflammatory bowel disease. Curr Opin Gastroenterol 2007; 23:370-378.