BIOCHEMICAL-STUDIES OF N-METHYLTRANSFERASE IN HUMAN AND GUINEA-PIG LUNG - NO APPARENT ROLE IN THE PATHOGENESIS OF ASTHMA

N-Methyltransferase activity was measured in surgical specimens of human lung using phenylethanolamine as substrate. Thirty-three male and seven female patients, age range 19-78 (median 62.5) years were studied. The activity in lung homogenates was 0.59 .times. 10-6 units/mg of protein (SEM 0.03, n = 40), with a range of 0.16-1.16 .times. 10-6 units/mg of protein. There was no difference (P = 0.97) in activity between males and females. Non-specific N-methyltransferase activity was estimated in 17 of the surgical specimens using .beta.-phenylethylamine as substrate. This activity was 38.9% (SEM 5.3) of that with phenylethanolamine. Comparative studies with rabbit lung, which has a well-characterized non-specific N-methyltransferase, showed significant differences in substrate specificity between the two species. The apparent Km and Vmax for phenylethanolamine in seven human lung homogenates was 22.0 (SEM 4.6), mmol/l and 1.82 .times. 10-6 units/mg of protein (SEM 0.36). The noradrenaline N-methyltransferase (NMT; EC 2.1.1.28) inhibitors SKF 64139-A and LY 134046 did not inhibit this activity up to a concentration of 100 .mu.mol/l. This activity was inhibited 51.4% (SEM 8.6, n = 6) by 100 .mu.mol/l S-adenosyl-L-homocysteine. Immunohistochemistry did not reveal immunoreactive NMT in human lung sections. Comparative studies with guinea-pig lung homogenates demonstrated non-specific N-methyltransferase activity in this species which is similar to the human lung. Using an ovalbumin-sensitized guinea-pig model of allergic bronchoconstriction, there was no difference (P = 0.24) between control (2.74 .times. 10-6 units/mg of protein, SEM 0.25, n = 5) and sensitized (2.24 .times. 10-6 units/mg of protein, SEM 0.27, n = 9) guinea pigs. These results show that human lung has significant N-methylating activity. This is not NMT but a nonspecific N-methyltransferase. There was no difference (P = 0.34) in activity between asthmatic and nonasthmatic lung. The animal model did not reveal a relationship between this activity and the development of allergic bronchoconstriction.