Localization of organic cation transporters OCT1 and OCT2 in rat kidney

Abstract

Renal excretion and reabsorption of organic cations are mediated by electrogenic and electroneutral organic cation transporters, which belong to a recently discovered family of polyspecific transporters. These transporters are electrogenic and exhibit differences in substrate specificity. In rat, the renal expression of the polyspecific cation transporters rOCT1 and rOCT2 was investigated. By in situ hybridization, significant amounts of both rOCT1 and rOCT2 mRNA were detected in S1, S2, and S3 segments of proximal tubules. By immunohistochemistry, expression of the rOCT1 protein was mainly observed in S1 and S2 segments of proximal tubules, with lower expression levels in the S3 segments. At variance, rOCT2 protein was mainly expressed in the S2 and S3 segments. Both transporters were localized to the basolateral cell membrane. Neither rOCT1 nor rOCT2 was detected in the vasculature, the glomeruli, and nephron segments other than proximal tubules. The data suggest that rOCT1 and rOCT2 are responsible for basolateral cation uptake in the proximal tubule, which represents the first step in cation secretion.

Membrane localization and pH-dependent transport of a newly cloned organic cation transporter (PMAT) in kidney cells

“…In well-differentiated MDCK cells, immunostaining of untagged PMAT and confocal imaging of YFP-tagged PMAT clearly demonstrated that PMAT protein is targeted to the apical membranes of these polarized kidney cells, suggesting that PMAT may be involved in luminal transport of organic cations. The apical localization of PMAT in polarized kidney cells is different from that of OCT1 and OCT2, which are localized to the basolateral membranes in MDCK cells and renal proximal tubules (7,15,18). These data suggest that although PMAT and OCTs share a large substrate overlap in transporting organic cations (4), they play different physiological roles in organic cation transport in the kidney.…”

Down-regulation of the organic cation transporter 1 of rat liver in obstructive cholestasis

“…To determine whether the expression of Oct1 is altered at the protein level in obstructive cholestasis in livers and kidneys, Western analysis was performed in total membrane fractions of these tissues obtained from non-operated and sham-operated controls and BDL rats. The protein blots, probed with the polyclonal anti-Oct1 antibody, 10,12 identified bands at 50 and 70 kilodaltons (Figs. 1A, 1B, 2A, 3A).…”

“…9 In contrast, Oct1 did not transport larger organic cations type II whose hepatic uptake 9 seems to be primarily a function of the organic anion-transporting polypeptide 2 (Oatp2, Slc21a5). 3 In rodents, Oct1 is expressed at the basolateral membranes of hepatocytes, 10 proximal renal tubules, 11,12 and enterocytes, 5 whereas in humans it is expressed mainly in the liver. 13,14 While Oct1 messenger RNA (mRNA) is distributed throughout the liver lobule, the expression of Oct1 protein is only observed in hepatocytes surrounding the central veins.…”

“…13,14 While Oct1 messenger RNA (mRNA) is distributed throughout the liver lobule, the expression of Oct1 protein is only observed in hepatocytes surrounding the central veins. 10 Several additional members of the Oct family have now been identified, including Oct2 (Slc22a2), 12,15 Oct3 (Slc22a3), 16 and the more distantly related novel proton/organic cation transporters (Octn) Octn1 (Slc22a4) 17 and Octn2 (Slc22a5). 18 However, Oct2 is almost exclusively expressed in the basolateral membranes of proximal renal tubules and has some overlap in substrate specificity with Oct1, 12,15 whereas Oct3 seems to be mainly expressed in the placenta and shows less overlap in substrate specificity with Oct1.…”

“…10 Several additional members of the Oct family have now been identified, including Oct2 (Slc22a2), 12,15 Oct3 (Slc22a3), 16 and the more distantly related novel proton/organic cation transporters (Octn) Octn1 (Slc22a4) 17 and Octn2 (Slc22a5). 18 However, Oct2 is almost exclusively expressed in the basolateral membranes of proximal renal tubules and has some overlap in substrate specificity with Oct1, 12,15 whereas Oct3 seems to be mainly expressed in the placenta and shows less overlap in substrate specificity with Oct1. 16 Recent studies in Oct1 knockout mice further suggest that Oct1 is the major if not the only physiologically significant hepatic uptake system for small organic cations.…”