title: [Lack of effect of cicletanine and its sulfoconjugated metabolite on the thiazide receptor expressed in Xenopus oocytes].
abstract: Although the renal receptor at which cicletanine acts is unknown, cicletanine was assumed to act like thiazide diuretics. Here we tested cicletanine and its natriuretic metabolite, cicletanine-sulfate, for inhibitory activity against the thiazide-sensitive NaCl cotransporter expressed in Xenopus oocytes. The renal thiazide-sensitive NaCl cotransporter was expressed in Xenopus laevis oocytes injected with rat cRNA TSCr (TSCr: thiazide-sensitive cotransporter from rat kidney) and both, racemic (+/-) cicletanine and its sulfoconjugated metabolite were tested for inhibitory activity against oocyte 22Na+ uptake catalyzed by this cotransporter. Polythiazide was used as reference thiazide. Polythiazide fully inhibited NaCl cotransporter function with IC50 approximately 1.2 x 10(-7) M. Conversely, neither cicletanine, nor cicletanine sulfate were able to inhibit such cotransporter, i.e.: a minimum concentration of 10(-4) M of cicletanine was necessary to induce a slight cotransporter inhibition (29.5 +/- 18.2%). Cicletanine sulfate was inactive, even at 10(-4) M.
  
  
  CONCLUSIONS
  (i) the natriuretic metabolite of cicletanine (cicletanine sulfate) is unable to inhibit thiazide-sensitive NaCl cotransporter and (ii) inhibition of such cotransporter by cicletanine required concentrations equal or higher than 10(-4) M--concentrations much more higher than urinary therapeutic ones in humans (approximately 10(-6) M). These results clearly demonstrate that cicletanine does not act like thiazide diuretics.
authors.affiliation: Instituto de Investigaciones Biomedicas, Universidad Nacional Autõnoma de México, Tlalpan.
authors.forename: A
authors.initials: A
authors.lastname: Monroy
authors.forename: C
authors.initials: C
authors.lastname: Plata
authors.forename: G
authors.initials: G
authors.lastname: Gamba
authors.forename: M T
authors.initials: MT
authors.lastname: Droy-Lefaix
authors.forename: R P
authors.initials: RP
authors.lastname: Garay
mesh_terms: D000818:Animals; D001581:Benzothiadiazines; D002352:Carrier Proteins / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D009865:Oocytes / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011955:Receptors, Drug / Q000187:drug effects*; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*; D049992:Sodium Chloride Symporters; D012979:Sodium Radioisotopes; D027981:Symporters; D014982:Xenopus laevis
chemical_list: D001581:Benzothiadiazines; D002352:Carrier Proteins; D004232:Diuretics; D011725:Pyridines; D011955:Receptors, Drug; D049993:Sodium Chloride Symporter Inhibitors; D049992:Sodium Chloride Symporters; D012979:Sodium Radioisotopes; D027981:Symporters; C064415:thiazide receptor; C077249:cycletanide sulfate; C038068:cicletanine