ISSN:
1432-1912
Keywords:
Halothane
;
Carbon Tetrachloride
;
Microsomal Metabolism
;
Cytochrome P-450
;
Covalent Protein Binding
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 1. In suspensions of rabbit liver microsomes reduced by dithionite or NADPH, halothane produces a difference absorption spectrum with a maximum at 473 nm and a minimum at 408 nm. The “optical affinity” (K s) was in the region of 3–6×10−6 M for dithionite reduced microsomes. The maximal absorption with dithionite reduced microsomes for halothane (473–550 nm) was 0.017–0.019 and for CCl4 (454–500 nm) 0.04–0.05 per nmol of cytochrome P-450. The appearance of the difference absorption with halothane is faster than that with CCl4. 2. During anaerobic incubation with NADPH-reduced liver microsomes from phenobarbital pretreated rabbits, 14C-labelled halothane (1 mM) was covalently bound to microsomal proteins at a rate of 2 nmol/mg protein in 30 min (CCl4: 11 nmol/mg protein in 30 min). Reduction by dithionite was ineffective. The binding of halothane was 60% inhibited in a gas phase of air, 75% by CO, 55% in the presence of 1 mM metyrapone, 50% by CCl4, but only 20% by red. glutathione. The binding of the radioactivity from labelled halothane and CCl4 to proteins of isolated rabbit lung and kidney microsomes was approximately proportional to the concentrations of cytochrome P-450 in the organ fractions. 3. Like CCl4, halothane (1 mM) inhibited several microsomal drug oxidation reactions. 4. Irreversible binding of halothane or its metabolite(s) to endoplasmic proteins might be connected with halothane liver damage.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00502066
Permalink