Ambroxol as an inhibitor of nitric oxide-dependent activation of soluble guanylate cyclase.
The influence of ambroxol on the activity of human platelet soluble guanylate cyclase and rat lung soluble guanylate cyclase was investigated. Ambroxol in the concentration range from 0.1 to 10 microM had no effect on the basal activity of both enzymes and slightly enhanced it at 50 and 100 microM. Ambroxol inhibited in a concentration-dependent manner the sodium nitroprusside-induced activation of both enzymes. The IC(50) values for inhibition by ambroxol of sodium nitroprusside-stimulated human platelet soluble guanylate cyclase and rat lung soluble guanylate cyclase were 3.9 and 2.1 microM, respectively. Ambroxol did not influence the stimulation of soluble guanylate cyclase by protoporphyrin 1X. Thus, it is possible that the molecular mechanism of the therapeutic action of ambroxol involves the inhibition of nitric oxide (NO)-dependent activation of soluble guanylate cyclase.
Severina
I S
IS
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, 10 Pogodinskaya str., 119832, Moscow, Russia. inst.@ibmh.msk.su
Bussygina
O G
OG
Pyatakova
N V
NV
Khropov
Y V
YV
Krasnoperov
R A
RA
D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005100:Expectorants / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D005100:Expectorants; D014665:Vasodilator Agents; D009599:Nitroprusside; D002084:Butylated Hydroxytoluene; D000551:Ambroxol; D009569:Nitric Oxide; D006162:Guanylate Cyclase