Biochemical studies of N-methyltransferase in human and guinea-pig lung: no apparent role in the pathogenesis of asthma.
1. 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 x 10(-6) units/mg of protein (SEM 0.03, n = 40), with a range of 0.16-1.16 x 10(-6) units/mg of protein. There was no difference (P = 0.97) in activity between males and females. 2. 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. 3. The apparent Km and Vmax for phenylethanolamine in seven human lung homogenates was 22.0 (SEM 4.6).mmol/l and 1.82 x 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 mumol/l. This activity was inhibited 51.4% (SEM 8.6, n = 6) by 100 mumol/l S-adenosyl-L-homocysteine. Immunohistochemistry did not reveal immunoreactive NMT in human lung sections. 4. Comparative studies with guinea-pig lung homogenates demonstrated non-specific N-methyltransferase activity in this species which is similar to the human lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Henderson
G D
GD
Department of Medicine, Flinders Medical Centre, Adelaide, Australia.
Ruffin
R E
RE
Alpers
J H
JH
Crockett
A J
AJ
Schembri
D A
DA
Latimer
K M
KM
D015078:2-Hydroxyphenethylamine / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000209:etiology; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008168:Lung / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D010627:Phenethylamines / Q000378:metabolism; D011817:Rabbits
D010627:Phenethylamines; D015078:2-Hydroxyphenethylamine; D008780:Methyltransferases