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01-11-2012 | Editorial

May the Truth Be with You: Lubiprostone as EP Receptor Agonist/ClC-2 Internalizing “Inhibitor”

Authors: Yasutada Akiba, Jonathan D. Kaunitz

Published in: Digestive Diseases and Sciences | Issue 11/2012

Excerpt

Chronic constipation is a common clinical problem. Lubiprostone, a bicyclic fatty acid derived from prostaglandin (PG) E₁, has been clinically used for the treatment of chronic constipation in adults. Camilleri et al. [1] first reported that lubiprostone inhibited gastric emptying, but accelerated small and large intestinal transit, which is associated with postprandial fullness. Subsequently, on the basis of clinical trials, investigators have reported a beneficial effect of lubiprostone in subjects with chronic constipation and functional bowel disease [2, 3]. …

Camilleri M, Bharucha AE, Ueno R, et al. Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2006;290:G942–G947.PubMedCrossRef

Johanson JF, Drossman DA, Panas R, Wahle A, Ueno R. Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2008;27:685–696.PubMedCrossRef

Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome—results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther. 2009;29:329–341.PubMedCrossRef

Cuppoletti J, Malinowska DH, Tewari KP, et al. SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents. Am J Physiol Cell Physiol. 2004;287:C1173–C1183.PubMedCrossRef

Foskett JK. ClC and CFTR chloride channel gating. Annu Rev Physiol. 1998;60:689–717.PubMedCrossRef

White MB, Amos J, Hsu JM, Gerrard B, Finn P, Dean M. A frame-shift mutation in the cystic fibrosis gene. Nature. 1990;344:665–667.PubMedCrossRef

Jentsch TJ, Neagoe I, Scheel O. CLC chloride channels and transporters. Curr Opin Neurobiol. 2005;15:319–325.PubMedCrossRef

Thiemann A, Grunder S, Pusch M, Jentsch TJ. A chloride channel widely expressed in epithelial and non-epithelial cells. Nature. 1992;356:57–60.PubMedCrossRef

Schwiebert EM, Cid-Soto LP, Stafford D, et al. Analysis of ClC-2 channels as an alternative pathway for chloride conduction in cystic fibrosis airway cells. Proc Natl Acad Sci USA. 1998;95:3879–3884.PubMedCrossRef

10.

Zdebik AA, Cuffe JE, Bertog M, Korbmacher C, Jentsch TJ. Additional disruption of the ClC-2 Cl⁻ channel does not exacerbate the cystic fibrosis phenotype of cystic fibrosis transmembrane conductance regulator mouse models. J Biol Chem. 2004;279:22276–22283.PubMedCrossRef

11.

Catalán MA, Flores CA, Gonzalez-Begne M, Zhang Y, Sepúlveda FV, Melvin JE. Severe defects in absorptive ion transport in distal colons of mice that lack ClC-2 channels. Gastroenterology. 2012;142:346–354.PubMedCentralPubMedCrossRef

12.

Catalán M, Cornejo I, Figueroa CD, Niemeyer MI, Sepúlveda FV, Cid LP. ClC-2 in guinea pig colon: mRNA, immunolabeling, and functional evidence for surface epithelium localization. Am J Physiol Gastrointest Liver Physiol. 2002;283:G1004–G1013.PubMed

13.

Lipecka J, Bali M, Thomas A, Fanen P, Edelman A, Fritsch J. Distribution of ClC-2 chloride channel in rat and human epithelial tissues. Am J Physiol Cell Physiol. 2002;282:C805–C816.PubMedCrossRef

14.

Catalán M, Niemeyer MI, Cid LP, Sepúlveda FV. Basolateral ClC-2 chloride channels in surface colon epithelium: regulation by a direct effect of intracellular chloride. Gastroenterology. 2004;126:1104–1114.PubMedCrossRef

15.

Peña-Múnzenmayer G, Catalán M, Cornejo I, et al. Basolateral localization of native ClC-2 chloride channels in absorptive intestinal epithelial cells and basolateral sorting encoded by a CBS-2 domain di-leucine motif. J Cell Sci. 2005;118:4243–4252.PubMedCrossRef

16.

Jentsch TJ. CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. Crit Rev Biochem Mol Biol. 2008;43:3–36.PubMedCrossRef

17.

Bassil AK, Borman RA, Jarvie EM, et al. Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon. Br J Pharmacol. 2008;154:126–135.PubMedCrossRef

18.

Cuthbert AW. Lubiprostone targets prostanoid EP₄ receptors in ovine airways. Br J Pharmacol. 2011;162:508–520.PubMedCrossRef

19.

Bijvelds MJ, Bot AG, Escher JC, De Jonge HR. Activation of intestinal Cl⁻ secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator. Gastroenterology. 2009;137:976–985.PubMedCrossRef

20.

Ao M, Venkatasubramanian J, Boonkaewwan C, et al. Lubiprostone activates Cl⁻ secretion via cAMP signaling and increases membrane CFTR in the human colon carcinoma cell line, T84. Dig Dis Sci. 2011;56:339–351.PubMedCrossRef

21.

Bao HF, Liu L, Self J, Duke BJ, Ueno R, Eaton DC. A synthetic prostone activates apical chloride channels in A6 epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2008;295:G234–G251.PubMedCrossRef

22.

Mizumori M, Akiba Y, Kaunitz JD. Lubiprostone stimulates duodenal bicarbonate secretion in rats. Dig Dis Sci. 2009;54:2063–2069.PubMedCentralPubMedCrossRef

23.

Fei G, Wang YZ, Liu S, et al. Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon. Am J Physiol Gastrointest Liver Physiol. 2009;296:G823–G832.PubMedCrossRef

24.

Sun X, Wang X, Wang GD, et al. Lubiprostone reverses the inhibitory action of morphine on mucosal secretion in human small intestine. Dig Dis Sci. 2011;56:330–338.PubMedCrossRef

25.

Jakab RL, Collaco AM, Ameen NA. Lubiprostone targets prostanoid signaling and promotes ion transporter trafficking, mucus exocytosis and contractility. Dig Dis Sci. 2012; (Epub ahead of print). doi:10.1007/s10620-012-2352-8.

26.

O’Brien CE, Anderson PJ, Stowe CD. Use of the chloride channel activator lubiprostone for constipation in adults with cystic fibrosis: a case series. Ann Pharmacother. 2010;44:577–581.PubMedCrossRef

27.

O’Brien CE, Anderson PJ, Stowe CD. Lubiprostone for constipation in adults with cystic fibrosis: a pilot study. Ann Pharmacother. 2011;45:1061–1066.PubMedCrossRef

28.

De Lisle RC, Mueller R, Roach E. Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype. BMC Gastroenterol. 2010;10:107.PubMedCentralPubMedCrossRef

29.

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.PubMedCentralPubMedCrossRef

30.

Lembo AJ, Johanson JF, Parkman HP, Rao SS, Miner PB Jr, Ueno R. Long-term safety and effectiveness of lubiprostone, a chloride channel (ClC-2) activator, in patients with chronic idiopathic constipation. Dig Dis Sci. 2011;56:2639–2645.PubMedCentralPubMedCrossRef

31.

Chamberlain SM, Rao SS. Safety evaluation of lubiprostone in the treatment of constipation and irritable bowel syndrome. Expert Opin Drug Saf. 2012;11:841–850.PubMedCrossRef

32.

Chey WD, Drossman DA, Johanson JF, Scott C, Panas RM, Ueno R. Safety and patient outcomes with lubiprostone for up to 52 weeks in patients with irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2012;35:587–599.PubMedCrossRef

Title: May the Truth Be with You: Lubiprostone as EP Receptor Agonist/ClC-2 Internalizing “Inhibitor”
Authors: Yasutada Akiba
Jonathan D. Kaunitz
Publication date: 01-11-2012
Publisher: Springer US
Published in: Digestive Diseases and Sciences / Issue 11/2012
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-012-2410-2

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