Inhibition of nitric oxide-dependent activation of soluble guanylyl cyclase by the antimalarial drug, artemisinin.
The influence of artemisinin on the activity of human platelet soluble guanylyl cyclase was investigated. Artemisinin (0.1-100 microM) had no effect on the basal activity of the enzyme. Artemisinin inhibited in a concentration-dependent manner the sodium nitroprusside-induced activation of human platelet guanylyl cyclase with an IC(50) value 5.6 microM. Artemisinin (10 microM) also inhibited (by 71+/-4.0%) the activation of the enzyme by the thiol-dependent nitric oxide (NO) donor, the derivative of furoxan, 3,4-dicyano-1,2,5-oxadiazole 2-oxide (10 microM), but did not influence the stimulation of soluble guanylyl cyclase by protoporphyrin 1X. Inhibition of guanylyl cyclase activation by NO donors but not by protoporphyrin 1X represents a possible additional mechanism of the pharmacological action of this drug.
Severina
Irina S
IS
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, 10 Pogodinskaya str. 119992, Moscow, Russia. inst.@ibmh.mask.su
Pyatakova
Natalya V
NV
Bussygina
Olga G
OG
Mikhailitsyn
Felix S
FS
Khropov
Yuri V
YV
D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins; D002374:Catalase / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology*; D012995:Solubility; D013482:Superoxide Dismutase / Q000494:pharmacology
D000962:Antimalarials; D037621:Artemisinins; D020030:Nitric Oxide Donors; D011524:Protoporphyrins; D012717:Sesquiterpenes; D009599:Nitroprusside; D009569:Nitric Oxide; C031327:artemisinin; C028025:protoporphyrin IX; D002374:Catalase; D013482:Superoxide Dismutase; D006162:Guanylate Cyclase