Transport of tyramine in short-term cultured rat liver parenchymal cells, endothelial cells and Kupffer cells

Abstract

In a previous report, we have shown that the uptake of tyramine in isolated rat liver parenchymal cells (PC) was mainly mediated by an active transport process in addition to a simple diffusion. Our present work demonstrates that both free diffusion and transporter-mediated processes for tyramine uptake also co-exist in liver endothelial cells (LEC) and Kupffer cells (KC). Kinetic analysis for the transport-mediated process shows that the K t (μM) and V max (pmol/mg of proteins/min or pmol/10 6 cells/min) for PC are 23.5 and 748.4 or 1197.4, those for LEC are 29.2 and 141.2 or 6.6, and for KC are 76.3 and 72.0 or 8.5. Benztropine and N-ethylmaleimide (NEM), a thiol-group modifier, which potentially inhibit the activity of tyramine transporter in PC, equally block tyramine transport in LEC and KC. Thus, cysteine(s) having free thiol group(s) could be associated with the normal function of these transporters. The increase (or decrease) of the interior negative membrane potential caused by NO 3 − and SCN − (or SO 3 2− ) stimulates (or inhibits) the transport activity, indicating that membrane potential is the immediate driving force for the entry of the amine into the three types of cells. In addition to these, an interior-to-exterior proton gradient stimulates the tyramine transport in these cells, consistent with H + exchange or OH- cotransport, suggesting that the transport process could be neutrogenic. Taking these results together indicates that the tyramine transporters existing in PC, LEC and KC bear quite similar characteristics. The diversity of the efficient uptake of tyramine among the three types of cells could result from the difference of the amounts of the transporters expressed in these cells. Therefore, PC is the main type of liver cells for the clearance of tyramine from the portal vein blood.