1 Histamine N-methyl transferase activity was measured in samples of human liver, brain, kidney, lung and intestinal mucosa. The mean (± s.d.) rate (nmol min-' mg-' protein) of histamine N-methylation was 1.78 ± 0.59 (liver, n = 60), 1.15 0.38 (renal cortex, n = 8), 0.79 ± 0.14 (renal medulla, n = 8), 0.35 0.08 (lung, n = 20), 0.47 ± 0.18 (human intestine, n = 30) and 0.29 ± 0.14 (brain, n = 13).
This study was designed to determine whether both enantiomers of chloroquine inhibit histamine N-methyltransferase. The mean estimates of IC50 for the d- and l-enantiomers of chloroquine were 4.9 and 17.8 microM (liver), respectively and 6.9 and 21.6 microM (brain), respectively. Ki estimates were significantly lower with d- than with l-chloroquine; hence, d-chloroquine interacts with the enzyme more effectively than l-chloroquine. If the adverse effects of chloroquine are due to the inhibition of histamine N-methyltransferase, therapy with the l-enantiomer might have lower toxicity. The residual activity of histamine N-methyltransferase should reflect both the degree of inhibition by chloroquine and the level of enzyme expression. The rate of histamine methylation was measured in 100 human liver samples and its range and fold of variation were 29% and threefold, respectively. Susceptibility to chloroquine should be greater in subjects with limited expression of histamine N-methyltransferase
1. The aim was to investigate the possibility of interindividual variability of histamine N-methyltransferase (HNMT) in the human liver and renal cortex. The activity of HNMT was measured in 99 specimens of the human liver and in 75 specimens of the renal cortex. 2. In the liver the activity of HNMT was positively skewed. It ranged 2.9-fold with a median of 1.72 pmol/min/mg. In the renal cortex the activity of HNMT was normally distributed and ranged 2.6-fold with a mean and coefficient of variation of 1.35 pmol/min/mg and 21%, respectively. 3. The activities of catechol methyltransferase and thiopurine methyltransferase were measured in the renal cortex and any correlations with HNMT activity were assessed. There was a weak but significant correlation (r = 0.294, p = 0.010) between HNMT and catechol methyltransferase activities whereas HNMT activity was not correlated with thiopurine methyltransferase activity. 4. These results are consistent with the view that HNMT is well expressed in the human liver and renal cortex and that it varies among subjects.
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