title: The effects of polyamines on human colonic mucosal function.
abstract: Electrogenic ion transport in human colon is a surrogate marker for colonic mucosal function, and may be manipulated by a variety of hormonal, neural, immune and paracrine mediators. Polyamines are present in vast quantities in the colonic lumen and appear to be integral to cellular function. This study explores some of the mechanisms of polyamine action on colonic tissue through study of their effects on differential secretory pathways, as well as examining their actions on intracellular cAMP and Ca(2+) accumulation. Human colonic mucosa was mounted in Ussing chambers and treated with polyamines (spermine, spermidine and putrescine) with changes in ion transport recorded. In separate experiments colonic crypts were treated with polyamines and intracellular cAMP levels determined by ELISA and intracellular calcium concentrations were quantified by fluorescent imaging. Polyamines at physiological concentrations (1mM) exert no effects on basal mucosal chloride secretion or transepithelial electrical resistance. Polyamines inhibit electrogenic ion secretion as stimulated by forskolin (cAMP-mediated), but not carbachol (Ach-mediated). All the polyamines used in this study inhibited intracellular cAMP accumulation, according to potency (spermine>spermidine>putrescine). Spermine increased intracellular Ca(2+) in a PKC-dependent manner, likely due to its effects on the extracellular calcium-sensing receptor (CaSR). Polyamines act to prevent cAMP-mediated Cl(-) hypersecretion in the colon, acting through CaSR to inhibit PKC-mediated [Ca(2+)]i release from intracellular stores.
authors.affiliation: Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland; School of Veterinary Medicine and Conway Institute of Biomolecular & Biomedical Science, University College Dublin, Dublin 4, Ireland. Electronic address: ailinrogers@gmail.com.
authors.forename: Ailín C
authors.initials: AC
authors.lastname: Rogers
authors.affiliation: Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland; School of Veterinary Medicine and Conway Institute of Biomolecular & Biomedical Science, University College Dublin, Dublin 4, Ireland.
authors.forename: Frank D
authors.initials: FD
authors.lastname: McDermott
authors.affiliation: Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland; School of Veterinary Medicine and Conway Institute of Biomolecular & Biomedical Science, University College Dublin, Dublin 4, Ireland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Mohan
authors.affiliation: Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: P Ronan
authors.initials: PR
authors.lastname: O'Connell
authors.affiliation: Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: Desmond C
authors.initials: DC
authors.lastname: Winter
authors.affiliation: School of Veterinary Medicine and Conway Institute of Biomolecular & Biomedical Science, University College Dublin, Dublin 4, Ireland.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Baird
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D013096:Spermine / Q000494:pharmacology
chemical_list: D011073:Polyamines; D013096:Spermine; D000242:Cyclic AMP; D002118:Calcium
keywords: Calcium-sensing receptor; Colon; Polyamines; Ussing chambers