Читать книгу Drug Transporters - Группа авторов - Страница 55

Similar to the OCTs, the zwitterion transporters are believed to function through the alternating‐access transport mechanism as detailed in Section 2.2.3. Multiple transport mechanisms have been observed for the OCTN transporters, depending on substrate. The zwitterion transporters can function as uniporters, like OCT1‐3, translocating single substrates, or as cotransporters, transporting multiple substrates in the same direction (symport) or opposite directions (antiport) (Fig. 2.2b) [17]. OCTN1 transports the zwitterion ergothioneine via a sodium‐dependent symport uptake mechanism, but can transport other zwitterions (e.g., gabapentin) independent of sodium. OCTN1 can also act as a pH‐dependent proton/cation antiporter (e.g., TEA), or a bidirectional organic cation uniporter (e.g., acetylcholine). OCTN2 acts as a secondary active sodium‐dependent cotransporter for carnitine, facilitating symport of sodium and carnitine at a 1:1 ratio [2]. OCTN2 transport of some cations, including TEA, is sodium‐independent, while other cations are transported via proton/cation antiport [2]. SLC22A15 transports zwitterions, notably ergothioneine, carnosine, and carnitine, and certain organic cations in a sodium‐dependent manner [79]. CT2 transport is very selective for L‐ and D‐carnitine, betaine, and TEA. Carnitine transport by CT2 is partially sodium‐dependent, with uptake reduced by 50% when sodium is replaced with lithium. Unlike SLC22A15, CT2 demonstrates pH‐dependent transport for carnitine.