Inhibition of histamine N-methyltransferase activity in guinea-pig pulmonary alveolar macrophages by nicotine

Abstract

Abstract Both S-(−)- and R-(+)-nicotine enantiomers are inhibitors of histamine Nτ-methylation activity in guinea-pig pulmonary alveolar macrophage cultures, exhibiting IC50 values of 7 and 8 μM, 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.