Organic phosphates as a new class of soluble guanylate cyclase inhibitors.
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.
Suzuki
T
T
Research Laboratory, Minophagen Pharmaceutical Co., Zama, Kanagawa, Japan. t-suzuki@sc.itc.keio.ac.jp
Suematsu
M
M
Makino
R
R
D019794:2,3-Diphosphoglycerate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002248:Carbon Monoxide / Q000494:pharmacology; D002417:Cattle; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010833:Phytic Acid / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D007191:Indazoles; D020030:Nitric Oxide Donors; D009943:Organophosphorus Compounds; C110881:S-nitro-N-acetylpenicillamine; D019794:2,3-Diphosphoglycerate; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009569:Nitric Oxide; D010833:Phytic Acid; D002248:Carbon Monoxide; D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase; D010396:Penicillamine