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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.

journal_name

Life Sci

journal_title

Life sciences

authors

Cai H,Batuman V,Puschett DB,Puschett JB

doi

10.1016/0024-3205(94)00567-2

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

839-45

issue

10

eissn

0024-3205

issn

1879-0631

pii

0024-3205(94)00567-2

journal_volume

55

pub_type

杂志文章

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