Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract

Life Sciences

Volumn 86, Issue 19-20, 2010, Pages 760-765

  Bryant, Alexander P ^a   Busby, Robert W ^a   Bartolini, Wilmin P ^a   Cordero, Etchell A ^a   Hannig, Gerhard ^a   Kessler, Marco M ^a   Pierce, Christine M ^a   Solinga, Robert M ^a   Tobin, Jenny V ^a   Mahajan Miklos, Shalina ^a   Cohen, Mitchell B ^b   Kurtz, Caroline B ^a   Currie, Mark G ^a  

^a IRONWOOD PHARMACEUTICALS INC   (United States)

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

Author keywords

Chronic constipation; Constipation predominant irritable bowel syndrome; Cyclic guanosine monophosphate; Guanylate cyclase C; Guanylin; Linaclotide; Uroguanylin

Indexed keywords

GUANYLATE CYCLASE INHIBITOR; LINACLOTIDE; UNCLASSIFIED DRUG; ENTEROTOXIN RECEPTOR; GASTROINTESTINAL AGENT; GUANYLATE CYCLASE; PEPTIDE; RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG POTENCY; DRUG STABILITY; FEMALE; GASTROINTESTINAL DISEASE; GASTROINTESTINAL TRACT FUNCTION; IN VITRO STUDY; IN VIVO STUDY; INTESTINE FLUID; INTESTINE MUCOSA; INTESTINE SECRETION; JEJUNUM; MALE; NONHUMAN; PHARMACODYNAMICS; ANIMAL; BIOAVAILABILITY; C57BL MOUSE; DOSE RESPONSE; DRUG EFFECT; DRUG POTENTIATION; GASTROINTESTINAL TRACT; GASTROINTESTINAL TRANSIT; GENETICS; METABOLISM; MOUSE; MOUSE MUTANT; ORAL DRUG ADMINISTRATION;

MUS; RODENTIA;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GASTROINTESTINAL AGENTS; GASTROINTESTINAL TRACT; GASTROINTESTINAL TRANSIT; GUANYLATE CYCLASE; INTESTINAL MUCOSA; INTESTINAL SECRETIONS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; PEPTIDES; RECEPTORS, PEPTIDE;

EID: 77951897011     PISSN: 00243205     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.lfs.2010.03.015     Document Type: Article

References (28)

1. Bouchoucha M., Devroede G., Dorvl E., Faye A., Arhan P., Arsac M. Different segmental transit times in patients with irritable bowel syndrome and "normal" colonic transit time: is there a correlation with symptoms?. Techniques in Coloproctology 2006, 10:287-296.
2. Busby R.W., Bryant A.P., Cordero E.A., Kessler M.M., Pierce C.M., Tobin J.V., Cohen M.B., Currie M.G. The molecular target of MD-1100 is guanylate cyclase C (GC-C), an apical receptor on intestinal epithelial cells. Gastroenterology 2005, 128(Suppl 2):A-464.
3. Crane M.R., Hugues M., O'Hanley P.D., Waldman S.A. Identification of two affinity states for low affinity receptors for Escherichia coli heat-stable enterotoxin: correlation of occupation of lower affinity state with guanylate cyclase activation. Molecular Pharmacology 1992, 41:1073-1080.
4. Drossman D.A. The functional gastrointestinal disorders and the Rome III process. Gastroenterology 2006, 130:1377-1390.
5. Eutamene H., Bradesi S., Larauche M., Theodorou V., Beaufrand C., Ohning G., Fioramonti J., Cohen M., Bryant A.P., Kurtz C., Currie M.G., Mayer E.A., Bueno L. Guanylate cyclase-C-mediated anti-nociceptive effects of linaclotide in rodent models of visceral pain. Neurogastroenterology and Motility 2009, 22:312--e84.
6. Fan X., Hamra F.K., Freeman R.H., Eber S.L., Krause W.J., Lim R.W., Pace V.M., Currie M.G., Forte L.R. Uroguanylin: cloning of preprouroguanylin cDNA, mRNA expression in the intestine and heart and isolation of uroguanylin and prouroguanylin from plasma. Biochemical and Biophysical Research Communications 1996, 219:457-462.
7. Forte L.R. Guanylin regulatory peptides: structures, biological activities mediated by cyclic GMP and pathobiology. Regulatory Peptides 1999, 81:25-39.
8. Hamra F.K., Eber S.L., Chin D.T., Currie M.G., Forte L.R. Regulation of intestinal uroguanylin/guanylin receptor-mediated responses by mucosal acidity. Proceedings of the National Academy of Sciences USA 1997, 94:2705-2710.
9. Hamra F.K., Fan X., Krause W.J., Freeman R.H., Chin D.T., Smith C.E., Currie M.G., Forte L.R. Prouroguanylin and proguanylin: purification from colon, structure, and modulation of bioactivity by proteases. Endocrinology 1996, 137:257-265.
10. Koch A., Voderholzer W.A., Klauser A.G., Mueller-Lissner S. Symptoms in chronic constipation. Diseases of the Colon and Rectum 1997, 40:902-906.
11. Li Z., Goy M.F. Peptide-regulated guanylate cyclase pathways in rat colon: in situ localization of GCA, GCC, and guanylin mRNA. American Journal of Physiology 1993, 265(2Pt1):G394-G402.
12. Mann E.A., Jump M.L., Wu J., Yee E., Gianella R.A. Mice lacking the guanylate cyclase C receptor are resistant to STa-induced intestinal secretion. Biochemical and Biophysical Research Communications 1997, 239:463-466.
13. Mayer E.A., Bradesi S., Chang L., Spiegel B.M.R., Bueller J.A., Naliboff B.D. Functional GI disorders: from animal models to drug development. Gut 2008, 57:384-404.
14. Pfeiffer A., Aszodi A., Seidler U., Ruth P., Hofmann F., Faessler R. Intestinal secretory defects and dwarfism in mice lacking cGMP-dependent protein kinase II. Science 1996, 274:2082-2085.
15. Rao S.P., Sellers Z., Crombie D.L., Hogan D.L., Mann E.A., Childs D., Keely S., Sheil-Puopolo M., Gianella R.A., Barrett K.E., Isenberg J.I., Pratha V.S. A role for guanylate cyclase C in acid-stimulated duodenal mucosal bicarbonate secretion. American Journal of Physiology - Gastrointestinal and Liver Physiology 2004, 286:95-101.
16. Sandler R.S., Drossman D.A. Bowel habits in young adults not seeking health care. Digestive Disease Science 1987, 32:841-845.
17. Schlossmann J., Feil R., Hofmann F. Insights into cGMP signaling derived from cGMP kinase knockout mice. Frontiers in Biosciences 2005, 10:1279-1289.
18. Schulz S., Green C.K., Yuen P.S.T., Garbers D.L. Guanylyl cyclase is a heat-stable enterotoxin receptor. Cell 1990, 63:941-948.
19. Schulz S., Lopez M.J., Kuhn M., Garbers D.L. Disruption of the guanylyl cyclase-C gene leads to a paradoxical phenotype of viable but heat-stable enterotoxin-resistant mice. Journal of Clinical Investigation 1997, 6:1590-1595.
20. - secretion. American Journal of Physiology 1997, 505:411-423.
21. - secretion via a novel GC-C- and CFTR-independent pathway. FASEB Journal 2008, 22:1-11.
22. Sindic A., Schlatter E. Cellular effects of guanylin and uroguanylin. Journal of the American Society of Nephrology 2006, 17:607-616.
23. Thiagarajah J.R., Broadbent T., Hsieh E., Verkman A.S. Prevention of toxin-induced intestinal ion and fluid secretion by a small-molecule CFTR inhibitor. Gastroenterology 2004, 126:511-519.
24. 125I-4Tyr and -18Tyr Escherichia coli heat-stable enterotoxin species purified by high-performance liquid chromatography. Analytical Biochemistry 1985, 148:26-36.
25. Vaandrager A.B. Structure and function of the heat-stable enterotoxin receptor/guanylyl cyclase C. Molecular and Cellular Biochemistry 2002, 230:73-83.
26. Vaandrager A.B., Smolenski A., Tilly C., Houtsmuller A.B., Ehlert E.M., Bot A.G., Edixhoven M., Boomaars W.E., Lohmann S.E., de Jonge H.R. Membrane targeting of cGMP-dependent protein kinase is required for cystic fibrosis transmembrane conductance regulator Cl- channel activation. Proceedings of the National Academy of Sciences USA 1998, 95:1466-1471.
27. Videlock E.J., Chang L. Irritable bowel syndrome: current approach to symptoms, evaluation, and treatment. Gastroenterology Clinics of North America 2007, 36:665-685.
28. Wiegand R.C., Kato J., Currie M.G. Rat guanylin cDNA: characterization of the precursor of an endogenous activator of intestinal guanylate cyclase. Biochemical and Biophysical Research Communications 1992, 185:812-817.