title: Cicletanine sulfate: inhibition of anion transport systems and natriuretic activity.
abstract: In contrast with cicletanine, its urinary sulfoconjugate metabolite (cicletanine sulfate) was active on membrane ion transport in human red blood cells. Cicletanine sulfate was a more potent inhibitor of the Na+ dependent [Cl-/HCO3-] exchanger (IC50 = 9 +/- 3 x 10(-5) mol/l; mean +/- SD of 4 experiments) than cicletanine (IC50 = 10(-3) mol/l). This inhibitory potency was intermediate between that of xipamide (IC50 = 2 x 10(-5) mol/l) and that of furosemide (IC50 = 2 x 10(-4) mol/l). Moreover, cicletanine sulfate exhibited modest inhibitory potency against the [Na+,K+,Cl-]-cotransport system (IC50 = 1 +/- 0.3 x 10(-3) mol/l; mean +/- SD of 4 experiments) and poor inhibitory activity against the [K+,Cl-]-cotransport system. Cicletanine sulfate was unable to modify the activity of Cl(-)-independent membrane carriers (Na+:H+ exchanger, Ca2+ pump, Na+:Li+ countertransport system and Na+,K+ pump). Following renal intraarterial administration in rats, cicletanine sulfate and not cicletanine, exhibited salidiuretic activity. In conclusion, the urinary sulfo-conjugate of cicletanine is an active anion transport inhibitor and natriuretic metabolite. In fact, this metabolite may be responsible for the salidiuretic action of cicletanine.
authors.affiliation: INSERM U@CNRS UA 130251, Faculté de Médicine, 8 Créteil, France.
authors.forename: R P
authors.initials: RP
authors.lastname: Garay
authors.forename: C
authors.initials: C
authors.lastname: Rosati
authors.forename: C
authors.initials: C
authors.lastname: Nazaret
authors.forename: A
authors.initials: A
authors.lastname: Esanu
authors.forename: T
authors.initials: T
authors.lastname: Tarrade
authors.forename: P
authors.initials: P
authors.lastname: Braquet
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D016623:Ion Pumps / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D009318:Natriuresis / Q000187:drug effects*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
chemical_list: D000959:Antihypertensive Agents; D016623:Ion Pumps; D011725:Pyridines; C077249:cycletanide sulfate; C038068:cicletanine