Naslov
Inhibition of human, mouse and horse cholinesterases by bambuterol enantiomers

Autori
Bosak, Anita ; Gazić, Ivana ; Vinković, Vladimir ; Kovarik, Zrinka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Congress of the Croatian Society of the Biochemistry and Molecular Biology on the occasion of the 30th Anniversary with international participation, Book of Abstracts / Kovarik, Zrinka - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2006

Skup
Congress of the Croatian Society of the Biochemistry and Molecular Biology on the occasion of the 30th Anniversary with international participation

Mjesto i datum
Vodice, Hrvatska, 03.10.2006. - 07.10.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
inhibition; cholinesterases; bambuterol; enantiomers

Sažetak
B2-adrenoceptor agonists (b2-agonists) are used as bronchodilators for the treatment of pulmonary disorders in human and veterinary medicine. They are usually used as racemates, but the bronchodilating effect of some b2-agonists has been associated mostly with the (R)-enantiomer. Bambuterol is a prodrug of terbutaline, a short-acting β 2-agonist. Since in vivo conversion of bambuterol involves hydrolysis by butyrylcholinesterase (BChE ; EC 3.1.1.8) via carbamoylation of BChE, which inhibits BChE, we studied the stereoselectivity and inhibition of human, mouse and horse BChE, as well as human and mouse acetylcholinesterase (AChE ; EC 3.1.1.7), by (R)- and (S)-bambuterol. The time course of inhibition was followed by measuring the enzyme activity using the Ellman's spectrophotometric method, and the rate constants of inhibition were calculated. AChE and BChE of the studied species were progressively inhibited by both enantiomers of bambuterol displaying a stereoselectivity with a preference for the (R)- over (S)-enantiomer, with the inhibition rate constant of (R)-enantiomer about five times faster than that of (S)-enantiomer. Inhibition rate constants for the studied BChEs ranged from 0.45 to 6.4&middot ; ; ; ; ; ; ; &micro ; ; ; ; ; ; ; M-1min-1 for (R)-bambuterol, and from 0.077 to 1.5 &micro ; ; ; ; ; ; ; M-1min-1for (S)-bambuterol. Bambuterol enantiomers were selective inhibitors of BChE, as it was previously shown for racemate (1), since BChE inhibition was at least 8000 times faster than respective AChE. We observed no significant species difference between human and mouse in bambuterol enantiomer inhibition that one might expect due to a high amino acid sequence. Bambuterol inhibition of horse BChE was about 14 times slower than for human and mouse BChE for (R)-, and about 18 times slower for (S)-bambuterol. The primary structure of horse BChE differs from the other two species in 15 amino acids. However, the inhibition of studied BChEs could only be accounted for by threonine at position 69, because it is located close to the peripheral site of BChE. (1) Kovarik Z. et al, Amino acids involved in the interaction of acetylcholinesterase and butyrylcholinesterase with the carbamates Ro 02-0683 and bambuterol, and with terbutalin, Biochim. Biophys. Acta 1999 (1422) 261-271.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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