title: Prostaglandin D2 regulates human colonic ion transport via the DP1 receptor.
abstract: OBJECTIVE
  Prostaglandin D2 is released by mast cells and is important in allergies. Its role in gastrointestinal function is not clearly defined. This study aimed to determine the effect of exogenous PGD2 on ion transport in ex vivo normal human colonic mucosa.
  
  
  METHODS
  Mucosal sheets were mounted in Ussing chambers and voltage clamped to zero electric potential. Ion transport was quantified as changes in short-circuit current. In separate experiments epithelial monolayers or colonic crypts, isolated by calcium chelation, were treated with PGD2 and cAMP levels determined by ELISA or calcium levels were determined by fluorimetry.
  
  
  RESULTS
  PGD2 caused a sustained, concentration-dependent rise in short-circuit current by increasing chloride secretion (EC50=376nM). This effect of PGD2 is mediated by the DP1 receptor, as the selective DP1 receptor antagonist BW A686C inhibited PGD2-induced but not PGE2-induced rise in short-circuit current. PGD2 also increased intracellular cAMP in isolated colonic crypts with no measurable influence on cytosolic calcium. PGD2 induces chloride secretion in isolated human colonic mucosa in a concentration-dependent manner with concomitant elevation of cytoplasmic cAMP in epithelial cells.
  
  
  CONCLUSIONS
  The involvement of DP2 receptor subtypes has not previously been considered in regulation of ion transport in human intestine. Since inflammatory stimuli may induce production of eicosanoids, selective regulation of these pathways may be pivotal in determining therapeutic strategies and in understanding disease.
authors.affiliation: Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland; UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute of Biomolecular & Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland; UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Medani
authors.affiliation: Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland; UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute of Biomolecular & Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland; UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Collins
authors.affiliation: Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland; UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute of Biomolecular & Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland; UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: H M
authors.initials: HM
authors.lastname: Mohan
authors.affiliation: UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute of Biomolecular & Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Walsh
authors.affiliation: Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland; UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: D C
authors.initials: DC
authors.lastname: Winter
authors.affiliation: UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute of Biomolecular & Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: alan.baird@ucd.ie.
authors.forename: A W
authors.initials: AW
authors.lastname: Baird
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002712:Chlorides; D006827:Hydantoins; D010975:Platelet Aggregation Inhibitors; D011982:Receptors, Prostaglandin; C501562:prostanoid D receptor 1, human; C058848:BW A868C; D000242:Cyclic AMP; D015230:Prostaglandin D2; D002118:Calcium
keywords: Colonic; Epithelium; Inflammation; Intestine; Ion transport; Prostaglandin D2; cAMP