Vaynshteyn David, Jeong Hyunyoung
Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA
Drug Metab Lett. 2012 Jun 1;6(2):116-9.
Caffeine is the active constituent in coffee. Continual consumption of caffeine can lead to an attenuated response also known as tolerance. Results from rat studies have shown that caffeine is an inducer of CYP1A2, the enzyme responsible for caffeine's metabolism. This suggests that CYP1A2 induction by caffeine may be in part responsible for caffeine tolerance. However, whether caffeine induces CYP1A2 expression in humans remains unknown. Our results from luciferase assays performed in HepG2 cells showed that caffeine is not an activator of the aromatic hydrocarbon receptor (AhR), a major transcription factor involved in upregulation of CYP1A2. Furthermore, caffeine did not induce CYP1A2 expression in primary human hepatocytes at a concentration attained by ordinary coffee drinking. On the other hand, caffeine enhanced CYP1A2 expression by 9-fold in rat hepatocytes. Our results suggest that caffeine from ordinary coffee drinking does not induce CYP1A2 expression in humans and that factors other than CYP1A2 induction by caffeine likely contribute to development of caffeine tolerance in humans.
咖啡因是咖啡中的活性成分。持续摄入咖啡因会导致反应减弱，即耐受性。大鼠研究结果表明，咖啡因是细胞色素P450 1A2（CYP1A2）的诱导剂，该酶负责咖啡因的代谢。这表明咖啡因诱导CYP1A2可能是咖啡因耐受性的部分原因。然而，咖啡因是否会在人体内诱导CYP1A2表达尚不清楚。我们在HepG2细胞中进行的荧光素酶测定结果表明，咖啡因不是芳烃受体（AhR）的激活剂，AhR是参与CYP1A2上调的主要转录因子。此外，在普通咖啡饮用所达到的浓度下，咖啡因不会在原代人肝细胞中诱导CYP1A2表达。另一方面，咖啡因可使大鼠肝细胞中的CYP1A2表达增加9倍。我们的结果表明，普通咖啡饮用中的咖啡因不会在人体内诱导CYP1A2表达，并且除了咖啡因诱导CYP1A2之外的其他因素可能导致人类咖啡因耐受性的发展。
