YC-1-like potentiation of NO-dependent activation of soluble guanylate cyclase by derivatives of protoporphyrin IX.
The influence of protoporphyrin IX derivatives--2,4-di(1-methoxyethyl)-deuteroporphyrin IX disodium salt (dimegin) and hematoporphyrin IX (HP)--on the activation of human platelet soluble guanylate cyclase by sodium nitroprusside was investigated. Dimegin and HP, like 1-benzyl-3-(hydroxymethyl-2-furyl)indazole (YC-1), produce synergistic effects on the activation of soluble guanylate cyclase by sodium nitroprusside. The synergistic activation of the enzyme by the combination of 10 microM sodium nitroprusside and 5 microM dimegin (or 5 microM HP) was 190 +/- 19 and 134 +/- 10%, respectively. The synergistic activation of guanylate cyclase by 3 microM YC-1 and 10 microM sodium nitroprusside was 255 +/- 19%. Dimegin and HP had no effect on the activation of guanylate cyclase by YC-1; they did not change the synergistic effect of YC-1 (3 microM) and sodium nitroprusside (10 microM) on guanylate cyclase activity. The synergistic activation of NO-stimulated guanylate cyclase activity by dimegin and HP represents a new biochemical effect of these compounds that may have important pharmacotherapeutic and physiological significance.
Severina
I S
IS
Orechovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia. irina.severina@ibmc.msk.ru
Pyatakova
N V
NV
Shchegolev
A Yu
AY
Ponomarev
G V
GV
D001792:Blood Platelets / Q000201:enzymology; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D007191:Indazoles / Q000378:metabolism*; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D009599:Nitroprusside / Q000378:metabolism; D011524:Protoporphyrins / Q000737:chemistry / Q000378:metabolism
D020536:Enzyme Activators; D007191:Indazoles; D020030:Nitric Oxide Donors; D011524:Protoporphyrins; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009599:Nitroprusside; D009569:Nitric Oxide; C028025:protoporphyrin IX; D006162:Guanylate Cyclase