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Pubmed ID :12439218
Publication Date : //

Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences.


By systematic mutation screening of the polyspecific organic cation transporter hOCT1 (SLC22A1) in 57 Caucasians, 25 genetic variations were identified and further analysed for population frequency. Five mutations resulting in the amino acid changes Arg61Cys, Cys88Arg, Phe160Leu, Gly401Ser, and Met420del, with respective allele frequencies of 9.1, 0.6, 22, 3.2, and 16%, were functionally characterized upon expression in Xenopus oocytes. Phe160Leu and Met420del exhibited substrate affinities and selectivites identical to hOCT1 wild-type. In contrast, uptake of 0.1 microm [3H]1-methyl-4-phenylpyridinium ([3H]MPP) by Arg61Cys, Cys88Arg and Gly401Ser were reduced to 30, 1.4 and 0.9% compared to wild-type, respectively. Since transport of 1 microm [3H]serotonin by Cys88Arg and Gly401Ser was reduced to only 13 and 12% of wild-type, these mutants exhibit a changed substrate selectivity. The data show that the mutants Arg61Cys, Cys88Arg and Gly401Ser could affect the disposition of OCT1 substrates and as a consequence may alter the duration and intensity of effects of drugs and neurotransmitters which are substrates for hOCT1.

Authors : Kerb Reinhold , Brinkmann Ulrich , Chatskaia Natalia , Gorbunov Dmitry , Gorboulev Valentin , Mornhinweg Esther , Keil Andrea , Eichelbaum Michel , Koepsell Hermann ,

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EIAAB36700 Apical organic cation transporter,OCT2,Organic cation transporter 2,Pig,SLC22A2,Solute carrier family 22 member 2,Sus scrofa
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EIAAB39151 Homo sapiens,Human,Liver-specific organic anion transporter 2,LST2,LST-2,OATP1B3,OATP-8,OATP8,SLC21A8,Organic anion transporter 8,Organic anion-transporting polypeptide 8,SLCO1B3,Solute carrier family
EIAAB36713 hOAT1,Homo sapiens,hPAHT,hROAT1,Human,OAT1,Organic anion transporter 1,PAH transporter,PAHT,Renal organic anion transporter 1,SLC22A6,Solute carrier family 22 member 6
KR071 Anti Rat Organic Cation Transporter 3 Polyclonal Antibody
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OCT31-S Anti_Rat Organic Cation Transporter 3 (OCT3) antiserum 1 100 ul
KR071 Anti Rat Organic Cation Transporter 3 Polyclonal Antibody
OCT31-A Anti-Rat Organic Cation Transporter 3 (OCT3) IgG #1, aff pure 100 ug
OCT11-P Rat Organic Cation Transporter 1 (OCT1) Control_blocking peptide 1 100 ug
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OCT11-S Anti_Rat Organic Cation Transporter 1 (OCT1) Antiserum 1 100 ul
OCT21-A Anti-Rat Organic Cation Transporter 2 (OCT2) IgG #1, aff pure 100 ug
OCT21-S Anti-Rat Organic Cation Transporter 2 (OCT2) antiserum #1 100 ul
OCT11-S Anti-Rat Organic Cation Transporter 1 (OCT1) Antiserum #1 100 ul
OCT31-P Rat Organic Cation Transporter 3 (OCT3) Control_blocking peptide 1 100 ug
OCT31-A Anti_Rat Organic Cation Transporter 3 (OCT3) IgG 1, aff pure 100 ug
OCT21-S Anti_Rat Organic Cation Transporter 2 (OCT2) antiserum 1 100 ul
OCT21-P Rat Organic Cation Transporter 2 (OCT2) Control_blocking peptide 1 100 ug
OCT21-A Anti_Rat Organic Cation Transporter 2 (OCT2) IgG 1, aff pure 100 ug
OCT11-A Anti-Rat Organic Cation Transporter 1 (OCT1) IgG #1, aff pure 100 ug


 

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