Inhibition of histamine N-methyltransferase activity in guinea-pig pulmonary alveolar macrophages by nicotine.
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.
Gairola
C
C
Tobacco and Health Research Institute, Lexington, KY.
Godin
C S
CS
Houdi
A A
AA
Crooks
P A
PA
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
D009538:Nicotine; D006632:Histamine; D008780:Methyltransferases; D006637:Histamine N-Methyltransferase