engleski

Inhibition of butyrylcholinesterase (EC 3.1.1.7) and acetylcholinesterase (EC 3.1.1.8) by terbutaline and bambuterol

The reversible inhibition by the bronchodilator terbutaline N-tert-butyl[2-(3, 5-dihydroxyphenyl)-2-hydroxyethyl]ammonium sulphate and the time course of inhibition by its bis-dimethylcarbamate prodrug, bambuterol, were followed by measuring the remaining enzyme activity with propionylthiocholine or acetylthiocholine as substrates. The aim of the study was to evaluate the rate of enzyme inhibition by bambuterol and the affinity of the leaving group terbutaline for three human serum butyrylcholinesterase genotypes: usual (UU), atypical (AA) and fluoride resistant (FS). The reaction was also measured on recombinantly derived mouse acetylcholinesterase (AChE w.t.) and mouse butyrylcholinesterase (BChE w.t.). Bambuterol inhibited the UU human BChE 70 times faster than the AA genotype. Also terbutaline had 13 times higher affinity for the UU than for the AA enzyme. Terbutaline had a 10 times higher affinity for the recombinant mouse BChE than for AChE. However, bambuterol inhibited mouse BChE about 15 000 times faster than AChE thus being among the most powerful specific inhibitors distinguishing BChE from AChE.

Bambuterol; terbutaline; reversible inhibition; progressive inhibition; human cholinesterase genotypes; recombinant mouse cholinesterase

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