rOCT2 is a basolateral potential-driven carrier, not an organic cation/proton exchanger.

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Sweet DH, Pritchard JB

rOCT2 is a basolateral potential-driven carrier, not an organic cation/proton exchanger.

Am J Physiol. 1999 Dec;277(6 Pt 2):F890-8.

PubMed ID

10600936 [ View in PubMed

]

Abstract

The driving forces mediating tetraethylammonium (TEA) transport were systematically assessed in Xenopus oocytes and MDCK cells expressing organic cation transporter (OCT) 2 cloned from rat kidney (rOCT2). In rOCT2 cRNA-injected oocytes, uptake of [14C]TEA was saturable, with an estimated Michaelis constant (Km) of 393 microM, and was specifically inhibited by organic cations. Furthermore, TEA uptake demonstrated two distinct components, one that was potential sensitive and one that was pH sensitive. When membrane potential was intact, TEA uptake was largely unaffected by changes in medium pH; when the oocyte membrane was depolarized (K+ in = out = 102.5 mM, plus valinomycin), decreasing external medium pH significantly reduced TEA uptake. Consistent with the potential sensitivity of uptake, electrophysiological analysis of rOCT2-injected oocytes demonstrated movement of positive charge into the oocyte upon TEA addition. To further evaluate the nature of the pH effect and assess the properties of rOCT2 in a renal epithelium, rOCT2 was introduced into MDCK cells. A stably transfected single cell clone (MDCK-rOCT2) showed mediated, potential-sensitive, pH-sensitive TEA uptake (Km = 48 microM). TEA efflux from preloaded MDCK-rOCT2 cells was stimulated by externally applied (trans) tetramethylammonium but was trans-inhibited by H+ (external pH 5.4). The effect of external H+ was to modulate rOCT2-mediated transport. Thus rOCT2 is a potential-driven transporter, not an organic cation/H+ exchanger, consistent with a physiological role in the basolateral entry step in renal organic cation secretion.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Quinacrine	Solute carrier family 22 member 2	Protein	Humans	Unknown	Inhibitor	Details
Quinine	Solute carrier family 22 member 2	Protein	Humans	Unknown	Inhibitor	Details