Abstract: The influence of ambroxol - a mucolytic drug - on the activity of human platelet soluble guanylate cyclase and rat lung soluble guanylate cyclase and activation of both enzymes by NO-donors (sodium nitroprusside and Sin-1) were investigated. Ambroxol in the concentration range from 0.1 to 10 μM had no effect on the basal activity of both enzymes. Ambroxol inhibited in a concentration-dependent manner the sodium nitroprusside-induced human platelet soluble guanylate cyclase and rat lung soluble guanylate cyclase with the IC50 values 3.9 and 2.1 μM, respectively. Ambroxol did not influence the stimulation of both enzymes by protoporphyrin IX.The influence of artemisinin - an antimalarial drug - on human platelet soluble guanylate cyclase activity and the enzyme activation by NO-donors were investigated. Artemisinin (0.1-100 μM) 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 guanylate cyclase with an IC50 value 5.6 μM. Artemisinin (10 μM) also inhibited (by 71±4.0%) the activation of the enzyme by thiol-dependent NO-donor the derivative of furoxan, 3,4-dicyano-1,2,5-oxadiazolo-2-oxide (10 μM), but did not influence the stimulation of soluble guanylate cyclase by protoporphyrin IX. It was concluded that the sygnalling system NO-soluble guanylate cyclase-cGMP is involved in the molecular mechanism of the therapeutic action of ambroxol and artemisinin.
Download PDF:
Reference: Pyatakova N.V., Severina I.S., Soluble guanylate cyclase in the molecular mechanism underlying the therapeutic action of drugs, Biomeditsinskaya khimiya, 2012, vol:
58(1), 32-42.
10. Kharitonov S.A., Yates D.H., Robbins R.A., Logan-Sinclar R., Sinebourne E., Barnes P.J. (1994) Am. J. Respir. Crit. Care Med., 150, 842-849. Scholar google search
19. Boldyrev А.А. (1998) v kn.: "Karnozin. Biologicheskoe znachenie i vozmozhnoe primenenie v meditsine" Iz-vo MGU, Moskva, cc. 252-269. Scholar google search
20. Babizhaev M.A. (2009) Drug Metabol. Drug Interact, 24(2-4), 275-323. Scholar google search
26. Farre N., Riffel B., Rudin W. (1999) Parasitology, 119, 139-143. Scholar google search
27. Dondorn A.M., Planche T., de-Bel E.E., Angus B.J., Chotivanich K.T., Silamut K., Rumijn J.A., Ruangvecrayuth R., Hoch F.J., Kager P.A., Vreeken J., White N.J. (1998) Am. J. Trop. Mol. Hyg., 59, 497-502. Scholar google search
28. Jones I.W., Thomsen L.L., Knowles R., Gutteridge W.E., Butcher G.A., Sinden R.E. (1996) Parasite Immunol., 18, 535-538. CrossRef Scholar google search
29. Jacobs P., Radzioch D., Stevenson M.M. (1995) J. Immunol., 155, 5306-5313. Scholar google search
30. Seguin M., Klitz F.M., Schneider I., Weir J.P., Goodbary M., Slayter M., Raney J.J., Aniadolu J.U., Green S.S.J. (1994) J. Exp. Med., 180, 353-358. CrossRef Scholar google search
32. Rockett K.A., Awburn M.M., Cowden W.B., Clark I.A. (1991) Infect. Immun., 59, 3280-3283. Scholar google search
33. Ghigo D., Todde R., Ginsburg H., Costamang C., Gautret R., Bussolino E., Ulliers D., Giribaldi G., Deharo E., Gabrielli G. (1995) J. Exp. Med., 182, 677-688. CrossRef Scholar google search
34. Taramelli D., Basilico N., Pagani E., Grande R., Monti D., Chione M., Olliaro P. (1995) Exp. Parasitol., 81, 501-511. CrossRef Scholar google search
35. Goldberg D., Slater A.F., Cerami A., Henderson G.B. (1990) Proc Natl. Acad. Sci. USA, 87, 2931-2935. CrossRef Scholar google search
52. Wink D.A., Vodovotz Y., Cook J.A., Krishna M.C., Kim S., Coffin D., DeGraff W., Dehica A.M., Liebman J., Mitchell J.B. (1998) Biochemistry (Moscow), 63, 802-809. Scholar google search
53. Cook J.A., Krishna M.C., Pacelli R., Kim S., DeGraff W., Gamson J., Vodovotz Y., Russa A., Mitchell J.B. (1997) Nitric Oxide, 1, 88-94. CrossRef Scholar google search
54. Jin Y., Heck D.E., DeGeorge G., Tian Y., Laskin J.D. (1996) Cancer Res., 56, 1978-1982. Scholar google search
55. Flamigni F., Facchini A., Stanie I., Tantini B., Bonavita F., Stefanelli C. (2001) Biochem. Pharmacol., 62, 319-328. CrossRef Scholar google search
