Organic phosphates as a new class of soluble guanylate cyclase inhibitors

FEBS Letters

Makino, Ryu²  Suzuki, Tsuneharu³  Suematsu, Makoto¹ 

[1]Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

[2]Department of Chemistry, College of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo 171-0021, Japan

[3]Research Laboratory, Minophagen Pharmaceutical Co., 2-2-3 Komatsubara, Zama, Kanagawa 228-0021, Japan

关键词: Soluble guanylate cyclase;    Nitric oxide;    Carbon monoxide;    Adenosine triphosphate;    Organic phosphate;    2;    3-Bisphosphoglyceric acid;   

DOI  :  10.1016/S0014-5793(01)02943-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

This study aimed to examine effects of varied organic phosphates on activities of soluble guanylate cyclase (sGC). The enzyme was purified from bovine lung. Physiologically relevant concentrations of ATP, 2,3-bisphosphoglyceric acid and inositol hexakisphosphate inhibited its enzyme activities under steady-state conditions as well as those determined under stimulation with S-nitroso-N-acetylpenicillamine, a nitric oxide donor, carbon monoxide or YC-1. Lineweaver–Burk plot analyses revealed that these three organic phosphates act as competitive inhibitors. Other organic phosphates such as cardiolipin and sphingomyelin but not inorganic phosphates exhibited such inhibitory actions. These results suggest that organic phosphates serve as inhibitors for sGC-dependent signaling events.

【 授权许可】

Unknown