title: Diphenylamine-2-carboxylic acid (DPC), Usually an inhibitor of Cl- and non-selective cation channels, inhibits Cl-/HCO3- exchange and opens Cl- and cation conductances in rabbit gallbladder epithelium.
abstract: In the apical plasma membrane of rabbit gallbladder epithelium various drugs (hydrochlorothiazide, phlorizin, phenylglyoxal) inhibit Cl-/HCO3- exchange and probably enhance the almost negligible intrinsic anion conductance of the exchanger. By radiochemical measurements of apical Cl- influx, the anion exchange is shown here to be directly and immediately inhibited by diphenylamine-2-carboxylic acid (DPC) too. Using conventional microelectrode techniques in intact tissue, DPC, with same dose/response curve, is shown to activate an apical anion conductance (GCl) that has similar properties and amplitude to the GCl activated by the other exchange inhibitors so far tested; the actions are not additive. Patch-clamp methods (cell-attached and excised inside-out patch configurations) reveal that GCl is due to anion channels that are non-rectifying, cytoplasm independent, sensitive to stilbene and dipyridamole and have conductance of a few picosiemens. All this strengthens the correlation between inhibition of anion exchange and the activation of GCl and channels with features similar to those of the almost negligible intrinsic anion conductance of the exchanger. Among the drugs tested, the effects of DPC and hydrochlorothiazide are even more similar, such that even their dose/response curves overlap. Moreover, both drugs also directly activate some verapamil-sensitive Ca2+ channels and consequently apamin-sensitive, Ca2+-activated K+ channels. Thus DPC, usually an inhibitor of Cl- and non-selective cation channels, is shown here to be capable of activating Cl- and cation conductances.
authors.affiliation: Dipartimento di Fisiologia e Biochimica Generali, Università degli Studi di Milano, Italy. fistrasp@mailserver.unimi.it
authors.forename: D
authors.initials: D
authors.lastname: Cremaschi
authors.forename: C
authors.initials: C
authors.lastname: Porta
authors.forename: G
authors.initials: G
authors.lastname: Meyer
authors.forename: C
authors.initials: C
authors.lastname: Sironi
authors.forename: M
authors.initials: M
authors.lastname: Garavaglia
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism; D001030:Apamin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D004232:Diuretics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005704:Gallbladder / Q000166:cytology / Q000378:metabolism*; D006852:Hydrochlorothiazide / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D000838:Anions; D002121:Calcium Channel Blockers; D002412:Cations; D018118:Chloride Channels; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D062367:ortho-Aminobenzoates; D006852:Hydrochlorothiazide; D001030:Apamin; C001209:fenamic acid; D014700:Verapamil