title: The bumetanide-resistant part of forskolin-induced anion secretion in rat colon.
abstract: In order to reveal the contribution of the Na(+)-K(+)-2 Cl(-)- cotransporter to forskolin-induced anion secretion, the inhibition of forskolin-stimulated short-circuit current (Isc) by bumetanide, furosemide, azosemide and piretanide was investigated. In the distal colon, all blockers inhibited the forskolin-stimulated Isc with a maximal efficiency of 70%. In contrast, in the proximal colon, bumetanide and furosemide inhibited only about 40% of the forskolin response, whereas piretanide and azosemide were ineffective. A similar result was observed, when Na+ was replaced by impermeant cations suggesting especially in the proximal colon a great part of forskolin-induced anion secretion to be independent of the Na(+)-K(+)-2 Cl(-)-cotransporter. In anion substitution experiments the forskolin-induced increase in Isc was reduced by 70-80%, if either Cl- or HCO3- were omitted from the buffer solution, whereas in the combined absence of both anions the response was nearly suppressed. Measurement of the mucosal alkalinization revealed that forskolin stimulated a HCO3- secretion, which was, however, too weak to explain the bumetanide-insensitive Isc induced by forskolin. Bumetanide inhibited the serosa-to-mucosa flux of Cl- (JsmCl) stimulated by forskolin; an effect, which was strongly enhanced by subsequent administration of the anion exchange inhibitor, SITS. These data suggest that the bumetanide-resistant part of the forskolin-induced Isc is mainly mediated by a basolateral anion exchanger, probably a Cl(-)-HCO3- exchanger, which contributes to forskolin-evoked Cl- secretion, and in addition by a small HCO3- secretion stimulated by the drug.
authors.affiliation: Institute for Veterinary Physiology, University of Giessen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Schultheiss
authors.forename: S
authors.initials: S
authors.lastname: Hörger
authors.forename: M
authors.initials: M
authors.lastname: Diener
mesh_terms: D000818:Animals; D017920:Antiporters / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology*; D003106:Colon / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D028021:Sodium-Potassium-Chloride Symporters; D013424:Sulfanilamides / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013777:Tetrazoles; D013876:Thiophenes; D000096926:Benzenesulfonamides
chemical_list: D017920:Antiporters; D001639:Bicarbonates; D002034:Bumetanide; D002352:Carrier Proteins; D018118:Chloride Channels; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D005576:Colforsin; D004232:Diuretics; D005665:Furosemide; D028021:Sodium-Potassium-Chloride Symporters; D013424:Sulfanilamides; D013449:Sulfonamides; C015451:piretanide; C018222:azosemide; D013777:Tetrazoles; D013876:Thiophenes; D000096926:Benzenesulfonamides