Ambroxol as an inhibitor of nitric oxide-dependent activation of soluble guanylate cyclase

The influence of ambroxol on the activity of human platelet soluble guanyla te cyclase and rat lung soluble guanylate cyclase was investigated. Ambroxo l in the concentration range from 0.1 to 10 muM had no effect on the basal activity of both enzymes and slightly enhanced it at 50 and 100 muM. Ambrox ol inhibited in a concentration-dependent manner the sodium nitroprusside-i nduced activation of both enzymes. The IC50 values for inhibition by ambrox ol of sodium nitroprusside-stimulated human platelet soluble guanylate cycl ase and rat lung soluble guanylate cyclase were 3.9 and 2.1 muM, respective ly. 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. (C) 2000 Elsevier Science B.V. All rights reserved.