Interindividual Diversity in Expression of Organic Anion Uptake Transporters in Normal and Cirrhotic Human Liver. Issue 5 (11th March 2020)

• Record Type: Journal Article
• Authors: Taniguchi, Tatsuya; Zanetti‐Yabur, Alana; Wang, Pijun; Usyk, Mykhaylo; Burk, Robert D.; Wolkoff, Allan W.
• Is Part Of: Hepatology communications. Volume 4:Issue 5(2020)
• Page Start: 739
• Page End: 752
• Publication Date: 2020-03-11
• Subjects: Hepatology -- Periodicals; Liver -- Diseases -- Periodicals; Liver Diseases; Gastroenterology; Periodicals; Fulltext; Internet Resources; Periodicals; 616.36
• DOI: 10.1002/hep4.1489
• Languages: English
• ISSNs: 2471-254X

Abstract

Abstract : The liver plays an essential role in removing endogenous and exogenous compounds from the circulation. This function is mediated by specific transporters, including members of the family of organic anion transport proteins (OATPs) and the Na + ‐taurocholate transporting polypeptide (NTCP). In the present study, transporter protein expression was determined in liver samples from patients with cirrhosis or controls without liver disease. Five transporters (OATP1A2, OATP1B1, OATP1B3, OATP2B1, and NTCP) were studied. Transporter content in homogenates of human liver was quantified on western blots probed with transporter‐specific antibodies in which a calibrated green fluorescent protein‐tagged transporter standard was included. Liver samples from 21 patients with cirrhosis (hepatitis C in 17 and alcohol abuse in 4) and 17 controls without liver disease were analyzed. Expression of each of the transporters had a large spread, varying by an order of magnitude in cirrhotic and control livers. OATP1B1 was the most abundant transporter in controls ( P < 0.01) but was significantly lower in cirrhotic livers as was NTCP expression ( P < 0.01). There was little difference in transporter expression with respect to age or sex. Despite the large variability in transporter expression within a group, analysis in individuals showed that those with high or low expression of one transporter had a similar magnitude in expression of the others. Conclusion: Differences in transporter expression could explain unanticipated heterogeneity of drug transport and metabolism in individuals with and without liver disease. Abstract : Tagged standards were used to immunologically quantify OATP1A2, OATP1B1, OATP1B3, OATP2B1 and NTCP in liver homogenates obtained from 21 patients with cirrhosis and 17 patients without liver disease. Despite as much as a ten‐fold range of expression of each transporter in the cohort, analysis in individuals showed that those with high or low expression of one transporter had high or low expression of each of the other transporters, suggesting a mechanism for the unpredictable heterogeneity of drug transport and metabolism between individuals.