title: Inhibition of histamine N-methyltransferase activity in guinea-pig pulmonary alveolar macrophages by nicotine.
abstract: Both S-(-)- and R-(+)-nicotine enantiomers are inhibitors of histamine N tau-methylation activity in guinea-pig pulmonary alveolar macrophage cultures, exhibiting IC50 values of 7 and 8 microM, respectively. S-(-)-Nicotine is not biotransformed under the conditions of the experiment, however, R-(+)-nicotine undergoes significant N-methylation to produce N-methylnicotinium ion. S-(-)-Nicotine appears to inhibit the N-methylation of its optical antipode by the alveolar nicotine N-methyltransferase. The results indicate that a contributing factor in the toxicology of cigarette smoke inhalation may be due to the inhibition of pulmonary metabolism of histamine by nicotine.
authors.affiliation: Tobacco and Health Research Institute, Lexington, KY.
authors.forename: C
authors.initials: C
authors.lastname: Gairola
authors.forename: C S
authors.initials: CS
authors.lastname: Godin
authors.forename: A A
authors.initials: AA
authors.lastname: Houdi
authors.forename: P A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000201:enzymology*; D013237:Stereoisomerism
chemical_list: D009538:Nicotine; D006632:Histamine; D008780:Methyltransferases; D006637:Histamine N-Methyltransferase