Taniguchi Yasuhito, Tonai-Kachi Hiroko, Shinjo Katsuhiro
Discovery Biology Research, Pfizer Global Research and Development, Nagoya Laboratories, Pfizer Inc., 5-2 Taketoyo, Aichi 470-2393, Japan.
FEBS Lett. 2006 Sep 18;580(21):5003-8. doi: 10.1016/j.febslet.2006.08.015. Epub 2006 Aug 17.
We found that zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, acted as an agonist for a G protein-coupled receptor, GPR35. In our intracellular calcium mobilization assay, zaprinast activated rat GPR35 strongly (geometric mean EC(50) value of 16nM), whereas it activated human GPR35 moderately (geometric mean EC(50) value of 840nM). We also demonstrated that GPR35 acted as a Galpha(i/o)- and Galpha(16)-coupled receptor for zaprinast when heterologously expressed in human embryonic kidney 293 (HEK 293) cells. These findings will facilitate the research on GPR35 and the drug discovery of the GPR35 modulators.
我们发现，扎普司特，一种著名的环磷酸鸟苷特异性磷酸二酯酶抑制剂，可作为G蛋白偶联受体GPR35的激动剂。在我们的细胞内钙动员试验中，扎普司特强烈激活大鼠GPR35（几何平均EC50值为16nM），而它对人GPR35的激活作用中等（几何平均EC50值为840nM）。我们还证明，当在人胚肾293（HEK 293）细胞中异源表达时，GPR35作为扎普司特的Gα(i/o)和Gα(16)偶联受体。这些发现将有助于GPR35的研究以及GPR35调节剂的药物发现。
