Hypochlorous acid is a potent inhibitor of acetylcholinesterase.
The role of hydrogen peroxide and peroxynitrite in the induction of airway hyperreactivity has been well described. Another reactive species which is formed during airway inflammation is hypochlorous acid (HOCl). In the present investigation the effect of HOCl on cholinergic innervation of the airway was investigated. It was observed that HOCl was capable of increasing the basal tension of electrically stimulated tracheal smooth muscle. It was found that HOCl inhibits purified acetylcholinesterase with an IC50 value of 0.66 microM. Decreased acetylcholinesterase activity could allow accumulation of acetylcholine and increased airway muscle tension. The effects of HOCl on the isolated organ and the enzyme preparation could be precluded with thiol group-containing compounds such as reduced glutathione and N-acetylcysteine. The present findings indicate that HOCl can act as inhibitor of acetylcholinesterase. The implications of this finding for the induction of airway hyperreactivity are discussed.
den Hartog
Gertjan J M
GJ
Department of Pharmacology and Toxicology, University Maastricht, P.O. Box 616, The Netherlands. gj.denhartog@farmaco.unimaas.nl
Vegt
Erik
E
van der Vijgh
Wim J F
WJ
Haenen
Guido R M M
GR
Bast
Aalt
A
D000110:Acetylcholinesterase / Q000378:metabolism*; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004558:Electric Stimulation; D005100:Expectorants / Q000494:pharmacology; D006168:Guinea Pigs; D006997:Hypochlorous Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects* / Q000294:innervation
D002800:Cholinesterase Inhibitors; D005100:Expectorants; D018727:Muscarinic Antagonists; D006997:Hypochlorous Acid; D001285:Atropine; D000110:Acetylcholinesterase; D000111:Acetylcysteine