N-methylation of phenylpyridines and bispyridyls as a potential toxication route: tissue distribution of azaheterocycle N-methyltransferase activity in the rabbit.

Abstract:

:The in vitro N-methylating capability of rabbit tissue cytosolic preparations, utilizing S-adenosyl-L-[methyl-3H]methionine as methyl donor, is described. Dialysed preparations from the lung, liver and kidney are capable of N-methylating 3- and 4-phenylpyridines and 3,3'- and 4,4'-bispyridyls; the corresponding 2-substituted derivatives are not substrates. With all the four substrates, azaheterocycle N-methyltransferase activity decreased in the order lung greater than kidney greater than liver; the activity in the lung was manifold greater than in the kidney and the liver. Azaheterocycle N-methyltransferase activity could not be detected in the brain cytosol under the enzyme assay conditions used. The production of N-methylpyridinium ion metabolites in the lung, from 4-phenylpyridine, 4,4'-bispyridyl and other pyridino-compounds present in tobacco smoke, may contribute to the observed pulmonary toxicity in tobacco users.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Godin CS,Crooks PA,Damani LA

doi

10.1016/0378-4274(86)90213-4

subject

Has Abstract

pub_date

1986-12-01 00:00:00

pages

217-22

issue

2-3

eissn

0378-4274

issn

1879-3169

pii

0378-4274(86)90213-4

journal_volume

34

pub_type

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