Enteropathogenic Escherichia coli infection inhibits intestinal serotonin transporter function and expression.

Section of Digestive Diseases and Nutrition, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Gastroenterology (Impact Factor: 12.82). 09/2009; 137(6):2074-83. DOI: 10.1053/j.gastro.2009.09.002
Source: PubMed

ABSTRACT Serotonin transporter (SERT) plays a critical role in regulating serotonin (5-hydroxytryptamine [5-HT]) availability in the gut. Elevated 5-HT levels are associated with diarrheal conditions such as irritable bowel syndrome and enteric infections. Whether alteration in SERT activity contributes to the pathophysiology of diarrhea induced by the food-borne pathogen enteropathogenic Escherichia coli (EPEC) is not known. The present studies examined the effects of EPEC infection on SERT activity and expression in intestinal epithelial cells and elucidated the underlying mechanisms.
Caco-2 cells as a model of human intestinal epithelia and EPEC-infected C57BL/6J mouse model of infection were utilized. SERT activity was measured as Na(+) and Cl(-) dependent (3)[H] 5-HT uptake. SERT expression was measured by real-time quantitative reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence studies.
Infection of Caco-2 cells with EPEC for 30-120 minutes decreased apical SERT activity (P < .001) in a type 3 secretion system dependent manner and via involvement of protein tyrosine phosphatases. EPEC infection decreased V(max) of the transporter; whereas cell surface biotinylation studies revealed no alteration in the cellular or plasma membrane content of SERT in Caco-2 cells. EPEC infection of mice (24 hours) reduced SERT immunostaining with a corresponding decrease in SERT messenger RNA levels, 5-HT uptake, and mucosal 5-HT content in the small intestine.
Our results demonstrate inhibition of SERT by EPEC and define the mechanisms underlying these effects. These data may aid in the development of a novel pharmacotherapy to modulate the serotonergic system in treatment of infectious diarrheal diseases.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diarrhea caused by enteric infections is a major factor in morbidity and mortality worldwide. An estimated 2-4 billion episodes of infectious diarrhea occur each year and are especially prevalent in infants. This review highlights the cellular and molecular mechanisms underlying diarrhea associated with the three classes of infectious agents, i.e., bacteria, viruses and parasites. Several bacterial pathogens have been chosen as model organisms, including Vibrio cholerae as a classical example of secretory diarrhea, Clostridium difficile and Shigella species as agents of inflammatory diarrhea and selected strains of pathogenic Escherichia coli (E. coli) to discuss the recent advances in alteration of epithelial ion absorption. Many of the recent studies addressing epithelial ion transport and barrier function have been carried out using viruses and parasites. Here, we focus on the rapidly developing field of viral diarrhea including rotavirus, norovirus and astrovirus infections. Finally we discuss Giardia lamblia and Entamoeba histolytica as examples of parasitic diarrhea. Parasites have a greater complexity than the other pathogens and are capable of creating molecules similar to those produced by the host, such as serotonin and PGE(2). The underlying mechanisms of infectious diarrhea discussed include alterations in ion transport and tight junctions as well as the virulence factors, which alter these processes either through direct effects or indirectly through inflammation and neurotransmitters.
    Gut Microbes 01/2010; 1(1):4-21.
  • [Show abstract] [Hide abstract]
    ABSTRACT: An approximate quantum-mechanical calculation is made of the energy of interaction of H— and He. The results are not of high accuracy, but serve to indicate the general nature of the interaction. This knowledge makes it possible to calculate more accurate values of the interaction from measured elastic scattering cross sections. The resultant interaction is combined with the previously known interaction of H and He to give an approximation to the inelastic (electron detachment) cross section, which is shown to be in reasonable agreement with experiment. The calculations emphasize the importance of the repulsion forces rather than the attraction forces. The accuracy of a correction for the finite width of the ion beam is also examined in some detail.
    The Journal of Chemical Physics 02/1958; 28(2). · 3.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diarrhea is a symptom common to a wide variety of gastrointestinal illnesses, and is an important public health challenge in underdeveloped regions of the world. Normal intestinal absorption is a complex process. Recent research offers new insights into normal physiology and pathophysiology. The role of the enteric nervous system and neurotransmitters in the pathogenesis of diarrhea in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) is being actively investigated. In patients with IBD, ileal and sigmoid biopsies showed altered transepithelial sodium and fluid transport, specifically from decreased expression of the NHE3, NHERF-1, and NHE1 epithelial Na channel. This results in changes in normal intestinal electroneutral NaCl absorption and may be an additional factor contributing to the diarrhea in patients with IBD. Physiologic studies in humans suggest that primary bile acid malabsorption may be caused by an abnormal feedback system resulting in the increased bile salts, which may explain the watery diarrhea. Finally, the role of zinc in treatment of infectious diarrhea led to studies of its effect on intracellular human enterocyte ion secretion. Understanding such basic mechanisms may lead to better and novel therapies for treatment of diarrhea.
    Current Gastroenterology Reports 08/2010; 12(4):236-41.