EFFECT OF KW-3902, A NOVEL ADENOSINE A(1) RECEPTOR ANTAGONIST, ON SODIUM-DEPENDENT PHOSPHATE AND GLUCOSE-TRANSPORT BY THE RAT RENAL PROXIMAL TUBULAR CELL

KW-3902, 1,3-dipropyl-8-(3-noradamantanyl)xanthine, is a novel potent and selective adenosine A(1)-receptor antagonist. KW-3902 has been fou nd to cause significant diuresis and natriuresis. To investigate the a ction of this adenosine A(1)-receptor antagonist on phosphate transpor t 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 mi nutes. The inhibitory effect was dose-dependent with maximum effect ac hieved 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 phosph ate uptake was 2 x 10(-6) M, Dixon plot analysis of the uptake data wa s consistent with pure non-competitive inhibition. The inhibition cons tant, K-i, 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 se milog dose response curve. Sodium-dependent glucose transport was not affected by KW-3902. These findings reveal that KW-3902 has a direct a nd specific inhibitory effect on phosphate uptake in renal proximal tu bules.