Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4185K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Li, C. Articles by Naren, A. P. Search for Related Content PubMed PubMed Citation Articles by Li, C. Articles by Naren, A. P. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Diarrhea Social Bookmarking                      What's this?

¹ Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163
² Department of Comparative Medicine, University of Tennessee Health Science Center, Memphis, TN 38163
³ Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Chicago, IL 60637

CORRESPONDENCE Anjaparavanda P. Naren: anaren{at}utmem.edu

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel localized primarily at the apical or luminal surfaces of epithelial cells that line the airway, gut, and exocrine glands; it is well established that CFTR plays a pivotal role in cholera toxin (CTX)-induced secretory diarrhea. Lysophosphatidic acid (LPA), a naturally occurring phospholipid present in blood and foods, has been reported to play a vital role in a variety of conditions involving gastrointestinal wound repair, apoptosis, inflammatory bowel disease, and diarrhea. Here we show, for the first time, that type 2 LPA receptors (LPA₂) are expressed at the apical surface of intestinal epithelial cells, where they form a macromolecular complex with Na⁺/H⁺ exchanger regulatory factor–2 and CFTR through a PSD95/Dlg/ZO-1–based interaction. LPA inhibited CFTR-dependent iodide efflux through LPA₂-mediated G_i pathway, and LPA inhibited CFTR-mediated short-circuit currents in a compartmentalized fashion. CFTR-dependent intestinal fluid secretion induced by CTX in mice was reduced substantially by LPA administration; disruption of this complex using a cell-permeant LPA₂-specific peptide reversed LPA₂-mediated inhibition. Thus, LPA-rich foods may represent an alternative method of treating certain forms of diarrhea.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Broere, N., Hillesheim, J., Tuo, B., Jorna, H., Houtsmuller, A. B., Shenolikar, S., Weinman, E. J., Donowitz, M., Seidler, U., de Jonge, H. R., Hogema, B. M. (2007). Cystic Fibrosis Transmembrane Conductance Regulator Activation Is Reduced in the Small Intestine of Na+/H+ Exchanger 3 Regulatory Factor 1 (NHERF-1)- but Not NHERF-2-deficient Mice. J. Biol. Chem. 282: 37575-37584 [Abstract] [Full Text]  
• Lin, F.-T., Lai, Y.-J., Makarova, N., Tigyi, G., Lin, W.-C. (2007). The Lysophosphatidic Acid 2 Receptor Mediates Down-regulation of Siva-1 to Promote Cell Survival. J. Biol. Chem. 282: 37759-37769 [Abstract] [Full Text]  
• Hama, K., Aoki, J., Inoue, A., Endo, T., Amano, T., Motoki, R., Kanai, M., Ye, X., Chun, J., Matsuki, N., Suzuki, H., Shibasaki, M., Arai, H. (2007). Embryo Spacing and Implantation Timing Are Differentially Regulated by LPA3-Mediated Lysophosphatidic Acid Signaling in Mice. Biol. Reprod. 77: 954-959 [Abstract] [Full Text]  
• Murph, M., Tanaka, T., Liu, S., Mills, G. B. (2006). Of Spiders and Crabs: The Emergence of Lysophospholipids and Their Metabolic Pathways as Targets for Therapy in Cancer.. Clin. Cancer Res. 12: 6598-6602 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS