Role of Anion Exchange Transporter PAT1 (SLC26A6) in Intestinal Absorption of Organic Anions

Abstract

Mouse PAT1 (putative anion transporter, CEFX, slc26a6), an orthologue of human SLC26A6, was recently identified at the intestinal brush-border membrane and shown to transport organic anions such as formate and oxalate, as well as inorganic ions. In this study, we conducted functional characterization of the uptake of formate by HEK293 cells transfected with PAT1. The uptake of formate by PAT1 was increased in the presence of an outwardly-directed Cl_- gradient, whereas Na₊ had no effect, and the uptake was independent of pH. The Km of PAT1 for formate was 3.75 mM. Various organic acids exhibited a cis-inhibitory effect on the uptake of formate by PAT1. Furthermore, the uptake was increased by preloading with _l-lactate, nicotinate, valproate and short-and medium-chain fatty acids, showing a trans-stimulatory effect. Thus, it was suggested that PAT1 transports organic acids as well as inorganic anions, demonstrating that it is involved in the intestinal absorption of anionic organic weak acids in the small intestine.

Keywords::

• Membrane transport
• Anion exchange transporter
• SLC26A6
• Intestinal absorption
• Organic anion
• Drug absorption