Kyerematen G A, Morgan M, Warner G, Martin L F, Vesell E S
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey 17033.
Biochem Pharmacol. 1990 Oct 15;40(8):1747-56. doi: 10.1016/0006-2952(90)90351-k.
The profile of nicotine metabolites produced by freshly isolated hepatocytes from rats, hamsters, guinea pigs, mice and humans was investigated after a 30-min exposure to nicotine ([2-14C]pyrrolidine). Large species differences occurred in the extent of nicotine metabolism; these ranged from 95% metabolism in guinea pig hepatocytes to only 30% metabolism in human and rat hepatocytes. The spectrum of metabolites formed also varied widely in different species. In hepatocytes from obese human subjects, nicotine was metabolized most extensively in smokers, least in nonsmokers, and to an intermediate degree in exsmokers, suggesting that cigarette smoking enhances the rate of nicotine metabolism. Pretreatment of all nonhuman species studied with phenobarbital and beta-naphthoflavone and with Aroclor in rats produced distinctive inductive patterns. Phenobarbital pretreatment of nonsmokers for 2 days prior to liver biopsy doubled the extent of nicotine conversion to cotinine by their hepatocytes. Rat and hamster hepatocytes exhibited sex and stereoselectivity differences in nicotine metabolism. Collectively, these studies indicate that hepatocytes offer some advantages over in vivo systems in investigating certain aspects of nicotine metabolism.
在将大鼠、仓鼠、豚鼠、小鼠和人类新鲜分离的肝细胞暴露于尼古丁（[2-¹⁴C]吡咯烷）30分钟后，对所产生的尼古丁代谢物谱进行了研究。尼古丁代谢程度存在很大的物种差异；范围从豚鼠肝细胞中95%的代谢到人类和大鼠肝细胞中仅30%的代谢。不同物种形成的代谢物谱也有很大差异。在肥胖人类受试者的肝细胞中，尼古丁在吸烟者中代谢最为广泛，在不吸烟者中代谢最少，在前吸烟者中代谢程度居中，这表明吸烟会提高尼古丁的代谢速率。用苯巴比妥和β-萘黄酮对所有研究的非人类物种进行预处理，并用多氯联苯混合物对大鼠进行预处理，产生了独特的诱导模式。在肝活检前2天，用苯巴比妥对不吸烟者进行预处理，可使他们的肝细胞将尼古丁转化为可替宁的程度增加一倍。大鼠和仓鼠肝细胞在尼古丁代谢方面表现出性别和立体选择性差异。总体而言，这些研究表明，在研究尼古丁代谢的某些方面时，肝细胞比体内系统具有一些优势。
