Arylsulphatase activity in liver and gastrointestinal tract of sheep [proceedings].

fugation as previously described (Berg & Gustafsson, 1974). Incubation with substrate and subsequent separation of the metabolites was performed by using a modification of the methods of von Bahr et al. (1977) for lignocaine and Bickel & Gigon (197 1) for imipramine. [methylene-14ClImipramine (2 x 1OSd.p.m., 560pg) or Icarbonyl-"Cllignocaine (2 x lo5 d.p.m., 200pg) was added to each incubation, which also contained an NADPH-regenerating system and approx. 6mg of microsomal protein. After extraction and separation of the metabolites by the previously published methods, the radioactive zones were located and quantified by either thin-layer scanning with a Beckman model 7230 radiochromatogram scanner or radioautography. The metabolites were initially identified by gas chromatography-mass spectrometry with authentic compounds as standards and subsequently by t.1.c. with authentic materials as standards. Two metabolites were found for lignocaine (the de-ethylated compound monoethylglycylxylidide and 3-hydroxylignocaine) and four major metabolites for imipramine (the demethylated compounds demethylimipramine and didemethylimipramine, imipramine N-oxide and 2-hydroxyimipramine). Sex differences were as found previously, i.e. dealkylation and N-oxidation were higher in males than females and hydroxylation tended to be lower in males. In intact males the Nde-ethylation of lignocaine was higher than in intact females (Table 1). Castration of male animals decreased the amount of Nde-ethylation, but not to the female level (0.9nmoVmin per mg of protein in castrated males, compared with 0.3nmoVmin per mg of protein in intact females). Ovariectomy had no effect on lignocaine Ndeethylation. Hypophysectomy of male animals had a simiiar effect to castration, but the effect of both operations was not additive, indicating that the &ect seen on hypophysectomy was the result of technical castration. Hypophysectomy of female animals, however, increased Nde-ethylase activity to the value for the castrated male. Taken overall these results indicate a role for the pituitary gland and the testes, but not the ovaries, in the control of hepatic microsomal drug metabolism. This is borne out by the results obtained for imipramine metabolism, where the Ndemethylase and N-oxidase activities follow the same pattern as that of the lignocaine Nde-ethylase activity. This dual control by androgen and the pituitary gland is very similar to that seen for the metabolism of steroids by the rat liver, indicating that the metabolism of drugs and steroids is controlled in a simiiar, if not identical, manner.