title: Effects of carbon monoxide on ion transport across rat distal colon.
abstract: The aim of the present study was to investigate whether carbon monoxide (CO) induces changes in ion transport across the distal colon of rats and to study the mechanisms involved. In Ussing chamber experiments, tricarbonyldichlororuthenium(II) dimer (CORM-2), a CO donor, evoked a concentration-dependent increase in short-circuit current (I(sc)). A maximal response was achieved at a concentration of 2.5·10(-4) mol/l. Repeated application of CORM-2 resulted in a pronounced desensitization of the tissue. Anion substitution experiments suggest that a secretion of Cl(-) and HCO(3)(-) underlie the CORM-2-induced current. Glibenclamide, a blocker of the apical cystic fibrosis transmembrane regulator channel, inhibited the I(sc) induced by the CO donor. Similarly, bumetanide, a blocker of the basolateral Na(+)-K(+)-2Cl(-) cotransporter, combined with 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid sodium salt, an inhibitor of the basolateral Cl(-)/HCO(3)(-) exchanger, inhibited the CORM-2-induced I(sc). Membrane permeabilization experiments indicated an activation of basolateral K(+) and apical Cl(-) channels by CORM-2. A partial inhibition by the neurotoxin, tetrodotoxin, suggests the involvement of secretomotor neurons in this response. In imaging experiments at fura-2-loaded colonic crypts, CORM-2 induced an increase of the cytosolic Ca(2+) concentration. This increase depended on the influx of extracellular Ca(2+), but not on the release of Ca(2+) from intracellular stores. Both enzymes for CO production, heme oxygenase I and II, are expressed in the colon as observed immunohistochemically and by RT-PCR. Consequently, endogenous CO might be a physiological modulator of colonic ion transport.
authors.affiliation: Institut für Veterinär-Physiologie, Universität Gieβen, Frankfurter Str. 100, 35392 Giessen, Germany. Martin.Diener@vetmed.uni-giessen.de
authors.forename: Julia
authors.initials: J
authors.lastname: Steidle
authors.forename: Martin
authors.initials: M
authors.lastname: Diener
mesh_terms: D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002248:Carbon Monoxide / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004553:Electric Conductivity; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D017136:Ion Transport; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology
chemical_list: D009942:Organometallic Compounds; D049994:Sodium Potassium Chloride Symporter Inhibitors; C447082:tricarbonyldichlororuthenium (II) dimer; D002034:Bumetanide; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D002118:Calcium