Clin Res Cardiol 96: Suppl 1 (2007)

V1478 - Expression, Localization and Regulation of Organic Cation Transporters in Human Heart
J. Haney1, M. Grube1, K. Meissner1, M. Böhm2, G. Jedlitschky1, H.K. Kroemer1
1Institut für Pharmakologie, Universität Greifswald, Greifswald; 2Innere Medizin III, Kardiologie und Angiologie, Universitätsklinikum des Saarlandes, Homburg/Saar;
Background: During the last years it became evident that drug transporters like P-glycoprotein and other members of the ABC-transporter family are not only expressed in cancer cells, biotransforming organs or physiological barriers, but also in other tissues like heart. It was further recognized that drug transport processes are not only dependent on efflux transporters, but also on uptake mechanisms mediated by special transport proteins. The uptake transporters relevant in drug uptake are divided into three major groups, the organic cation and anion transporters (OATs and OCT(N)s) and the organic anion transporting polypeptides (OATPs), which are responsible for the uptake of more bulky compounds. Because several OCT transporters have been shown to be involved in the uptake of cardiovascular drugs like verapamil and spironolactone as well as important endogenous compounds like carnitine, we decided to characterize the cardiac expression of OCT1, 2 and 3 as well as OCTN1 and 3.
Methods/Results: mRNA levels of OCT1, 2, 3 and OCTN1 were analyzed in heart samples by quantitative polymerase chain reaction. Samples were taken from patients with ischemic cardiomyopathy (ICM) and dilated nonischemic cardiomyopathy (DCM; n = 7 each) as well as from control hearts (NF) obtained from potential donors without any evidence of heart disease on medical history. OCT1 mRNA expression was reduced in the DCM and ICM samples, with expression levels of 62% and 61% of NF hearts, respectively. OCT2 mRNA could not be detected in human heart, while OCT3 mRNA expression was also slightly reduced in patients with cardiomyopathy (DCM: 78%, ICM: 67%).  A major difference however could be detected in the mRNA expression of the low affinity carnitine transporter OCTN1, which expression was decreased to 36 % for DCM and 82% for ICM samples as compared to NF hearts. For localization studies we used immunofluorescence microscopy revealing OCT1, 3 and OCTN1 to be mainly located in the vascular endothelium. In contrast, the OCTN3 protein was mainly detected in cardiomyocytes with only weak signals within the endothelial cells.
Conclusion: Taken together, mRNA expression of OCT1, 3 and OCTN1 could be demonstrated in human heart. Furthermore, OCTN3 could be detected on protein level. While OCT1, 3 and OCTN1 are mainly located to the vascular endothelium, OCTN3 was only found  in cardiomyocytes. With regard to a disease dependent expression we found OCT1, 3 and OCTN1 to be modulated by dilated and ischemic cardiomyopathy. The latter finding may be important with regard to cardiac uptake of cardiovascular drugs like verapamil administered to these patients.