Effect of KW-3902, a novel adenosine A sub(1) receptor antagonist, on sodium-dependent phosphate and glucose transport by the rat renal proximal tubular cell

• Published in: Life sciences (1973) Vol. 55; no. 10; pp. 839 - 845
• Main Authors: Cai, Hui, Batuman, V, Puschett, D B, Puschett, J B
• Format: Journal Article
• Language: English
• Published: 01.01.1994
• ISSN: 0024-3205

KW-3902, 1,3-dipropyl-8-(3-noradamantanyl)xanthine, is a novel potent and selective adenosine A sub(1)-receptor antagonist. KW-3902 has been found to cause significant diuresis and natriuresis. To investigate the action of this adenosine A sub(1)-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 super(-5) M in the uptake media. The half-maximal inhibitory concentration, IC sub(50), of KW-3902 on phosphate uptake was 2 x 10 super(-6) M. Dixon plot analysis of the uptake data was consistent with pure non-competitive inhibition. The inhibition constant, K sub(i), of 6.2 x 10 super(-6) M for phosphate transport, derived from the Dixon plot, was in close agreement with the IC sub(50) 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.