Stereoselective sulphate conjugation of salbutamol by human lung and bronchial epithelial cells.
1. The metabolism of (+)-, (-)- and (+/-)-salbutamol by sulphoconjugation was determined in vitro using human lung cytosol and bronchial epithelial BEAS-2B cell homogenate. 2. For the lungs the intrinsic clearance (Vmax/Km) value for the pharmacologically active (-)-salbutamol (0.49 +/- 0.32 ml min-1 g-1 protein) exceeded that of (+)-salbutamol (0.046 +/- 0.028 ml min-1 g-1 protein) by 11-fold. This was mainly due to a difference in Km value, which was 16 times higher for (+)-salbutamol (1300 +/- 170 microM) than for (-)-salbutamol (83 +/- 12 microM). 3. The stereoselectivity of sulphoconjugation of salbutamol was very similar in the BEAS-2B cells, although the absolute activity was considerably lower. 4. The enzyme catalyzing this reaction both in the lungs and in the BEAS-2B cells was the monoamine (M) form phenolsulphotransferase. 5. These observations emphasize that the smooth muscle of the bronchi most likely are exposed to considerably higher concentrations of the potentially toxic (+)-enantiomer than of the bronchodilating (-)-enantiomer during therapy with (+/-)-salbutamol.
Eaton
E A
EA
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425, USA.
Walle
U K
UK
Wilson
H M
HM
Aberg
G
G
Walle
T
T
D000420:Albuterol / Q000378:metabolism* / Q000494:pharmacology; D001980:Bronchi / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism*; D013237:Stereoisomerism
D000420:Albuterol