title: Effect of KW-3902, a novel adenosine A1 receptor antagonist, on sodium-dependent phosphate and glucose transport by the rat renal proximal tubular cell.
abstract: KW-3902, 1,3-dipropyl-8-(3-noradamantanyl)xanthine, is a novel potent and selective adenosine A1-receptor antagonist. KW-3902 has been found to cause significant diuresis and natriuresis. To investigate the action of this adenosine A1-receptor antagonist on phosphate transport in renal proximal tubular cells, we studied its effect on the uptake of phosphate by the cultured rat renal proximal tubular cell. KW-3902 significantly inhibited sodium-dependent uptake of phosphate at 10 minutes. The inhibitory effect was dose-dependent with maximum effect achieved at a KW-3902 concentration of 3 x 10(-5) M in the uptake media. The half-maximal inhibitory concentration, IC50, of KW-3902 on phosphate uptake was 2 x 10(-6) M. Dixon plot analysis of the uptake data was consistent with pure non-competitive inhibition. The inhibition constant, Ki, of 6.2 x 10(-6) M for phosphate transport, derived from the Dixon plot, was in close agreement with the IC50 calculated from a semilog dose response curve. Sodium-dependent glucose transport was not affected by KW-3902. These findings reveal that KW-3902 has a direct and specific inhibitory effect on phosphate uptake in renal proximal tubules.
authors.affiliation: Department of Medicine SL 12, Tulane University School of Medicine, New Orleans, Louisiana 70112-2699.
authors.forename: H
authors.initials: H
authors.lastname: Cai
authors.forename: V
authors.initials: V
authors.lastname: Batuman
authors.forename: D B
authors.initials: DB
authors.lastname: Puschett
authors.forename: J B
authors.initials: JB
authors.lastname: Puschett
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007700:Kinetics; D010695:Phlorhizin / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D010710:Phosphates; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C073525:rolofylline; D012964:Sodium; D010695:Phlorhizin; D005947:Glucose