title: Inhibition of basolateral cAMP permeability in the toad urinary bladder.
abstract: 1. The effect of sulphonylurea drugs on hydrosmotic flow across toad urinary bladder epithelium was re-evaluated in the present study. Glibenclamide, added to the basolateral medium, significantly enhanced the osmotic flow induced by low doses of antidiuretic hormone (ADH) or forskolin (FK), while it inhibited the effect of exogenous cyclic adenosine monophosphate (cAMP) or its non-hydrolysable bromo derivative, 8-Br-cAMP, added to the basolateral medium. These opposite effects of glibenclamide on the transepithelial osmotic flow can be explained by a reduction of cAMP permeability across the basolateral membrane of the epithelium. The decrease in cAMP permeability leads, according to the direction of the cAMP gradient, to firstly an enhanced osmotic flow when cAMP is generated intracellularly by addition of ADH and FK, glibenclamide reducing cAMP exit from the cell, and secondly a decreased osmotic flow in response to cAMP (and 8-Br-cAMP) added to the basolateral medium, glibenclamide inhibiting, in this case, their entry into the cell. 2. The demonstration that glibenclamide actually inhibits the basolateral cAMP permeability rests on the fact that firstly it decreases the release of cAMP into the basolateral medium by about 40 %, at each concentration of ADH or forskolin tested, secondly it increases the cAMP content of paired hemibladders incubated in the presence of ADH or FK, when intracellular degradation was prevented by phosphodiesterase inhibition, and thirdly it decreases also the uptake of basolateral 8-Br-[3H]cAMP into paired toad hemibladders. 3. Taken together, the present data demonstrate that glibenclamide inhibits the toad urinary bladder basolateral membrane permeability to cAMP, most probably by a direct interaction with a membrane protein not yet indentified but distinct from the sulphonylurea receptor.
authors.affiliation: Laboratoire de Physiopathologie, and Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucleaire, School of Medicine, Universite Libre de Bruxelles, Brussels, Belgium. aboom@ulb.ac.be
authors.forename: A
authors.initials: A
authors.lastname: Boom
authors.forename: P E
authors.initials: PE
authors.lastname: Golstein
authors.forename: M
authors.initials: M
authors.lastname: Frerotte
authors.forename: J V
authors.initials: JV
authors.lastname: Sande
authors.forename: R
authors.initials: R
authors.lastname: Beauwens
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000493:pharmacokinetics / Q000494:pharmacology; D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002024:Bufo marinus; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008560:Membrane Fluidity / Q000502:physiology; D009995:Osmosis / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D064233:Sulfonylurea Receptors; D001743:Urinary Bladder / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology; D014867:Water / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014665:Vasodilator Agents; D062367:ortho-Aminobenzoates; D014867:Water; D014667:Vasopressins; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D020110:Pinacidil; C001209:fenamic acid; D000242:Cyclic AMP; D005905:Glyburide