• Biochim. Biophys. Acta · Jul 1999

    Inhibitory effect of KW-3902, an adenosine A(1) receptor antagonist, on p-aminohippurate transport in OK cells.

    • J Nagai, I Yano, Y Habu, T Katsura, Y Hashimoto, and K Inui.
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
    • Biochim. Biophys. Acta. 1999 Jul 15; 1419 (2): 164-72.

    AbstractKW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine) is a novel potent and selective adenosine A(1) receptor antagonist. We examined the effect of KW-3902 on p-aminohippurate (PAH) transport in opossum kidney (OK) epithelial cells. Pretreatment for 3 h with KW-3902 inhibited the transcellular transport of PAH across OK cell monolayers from the basal to the apical side. The uptake of PAH across the basolateral membrane of OK cells was inhibited by KW-3902 pretreatment in a time- and concentration-dependent manner. A kinetic analysis revealed that the inhibitory effect of KW-3902 on the basolateral PAH uptake was due to an increase in the Michaelis constant (K(m)) as well as a decrease in the maximum uptake rate (V(max)), showing that the inhibition was a mixed type. Pretreatment with adenosine deaminase or 8-cyclopentyl-1,3-dipropylxanthine, another selective adenosine A(1) receptor antagonist, also decreased the basolateral PAH uptake. KW-3902 pretreatment had no effect on the concentration of intracellular alpha-ketoglutarate which exchanges for PAH across the basolateral membrane of OK cells. These results suggest that KW-3902 has an inhibitory effect on PAH transport in OK epithelial cells.

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