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Functional cooperation of URAT1 (SLC22A12) and URATv1 (SLC2A9) in renal reabsorption of urate.
Nephrol Dial Transplant. 2013 Mar; 28(3):603-11.ND

Abstract

BACKGROUND

Serum urate (SUA) level is affected by alteration in urinary reabsorption caused by clinically important drugs; however, there are no experimental models suitable to assess their effect on renal reabsorption. We, therefore, aimed to establish an experimental system co-expressing the urate transporters URAT1 (SLC22A12) and URATv1 (SLC2A9) (designated UUv cells) at the apical and basolateral membranes, respectively.

METHODS

Apical uptake and vectorial transport of [(14)C]urate in the apical-to-basolateral direction in UUv cells were measured in the presence or absence of uricosuric benzbromarone or anti-uricosuric trans-stimulators.

RESULTS

The urate permeability in the apical-to-basolateral direction remarkably increased by 7.0-fold in UUv cells, compared with non-transfected mock cells. The apical-to-basolateral transport was cis-inhibited by benzbromarone, but trans-stimulated by pyrazinecarboxylic acid and monocarboxylates such as nicotinate and lactate. Furthermore, salicylate showed both trans-stimulation and cis-inhibition in the urate transport at low and high concentrations, respectively. Finally, coexpression of URAT1 and URATv1 in human kidney epithelial cells was exhibited immunohistochemically.

CONCLUSIONS

It is demonstrated that functional cooperation of URAT1 and URATv1 is essential for renal reabsorption of urate, and in the established system influence of drugs on SUA is reflected in the alteration of urate permeability across the renal tubular epithelial cells.

Authors+Show Affiliations

Department of Membrane Transport and Biopharmaceutics, Kanazawa University, Kakuma-machi, Kanazawa , Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23291366

Citation

Nakanishi, Takeo, et al. "Functional Cooperation of URAT1 (SLC22A12) and URATv1 (SLC2A9) in Renal Reabsorption of Urate." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 28, no. 3, 2013, pp. 603-11.
Nakanishi T, Ohya K, Shimada S, et al. Functional cooperation of URAT1 (SLC22A12) and URATv1 (SLC2A9) in renal reabsorption of urate. Nephrol Dial Transplant. 2013;28(3):603-11.
Nakanishi, T., Ohya, K., Shimada, S., Anzai, N., & Tamai, I. (2013). Functional cooperation of URAT1 (SLC22A12) and URATv1 (SLC2A9) in renal reabsorption of urate. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 28(3), 603-11. https://doi.org/10.1093/ndt/gfs574
Nakanishi T, et al. Functional Cooperation of URAT1 (SLC22A12) and URATv1 (SLC2A9) in Renal Reabsorption of Urate. Nephrol Dial Transplant. 2013;28(3):603-11. PubMed PMID: 23291366.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional cooperation of URAT1 (SLC22A12) and URATv1 (SLC2A9) in renal reabsorption of urate. AU - Nakanishi,Takeo, AU - Ohya,Kouhei, AU - Shimada,Sho, AU - Anzai,Naohiko, AU - Tamai,Ikumi, Y1 - 2013/01/04/ PY - 2013/1/8/entrez PY - 2013/1/8/pubmed PY - 2013/9/27/medline SP - 603 EP - 11 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 28 IS - 3 N2 - BACKGROUND: Serum urate (SUA) level is affected by alteration in urinary reabsorption caused by clinically important drugs; however, there are no experimental models suitable to assess their effect on renal reabsorption. We, therefore, aimed to establish an experimental system co-expressing the urate transporters URAT1 (SLC22A12) and URATv1 (SLC2A9) (designated UUv cells) at the apical and basolateral membranes, respectively. METHODS: Apical uptake and vectorial transport of [(14)C]urate in the apical-to-basolateral direction in UUv cells were measured in the presence or absence of uricosuric benzbromarone or anti-uricosuric trans-stimulators. RESULTS: The urate permeability in the apical-to-basolateral direction remarkably increased by 7.0-fold in UUv cells, compared with non-transfected mock cells. The apical-to-basolateral transport was cis-inhibited by benzbromarone, but trans-stimulated by pyrazinecarboxylic acid and monocarboxylates such as nicotinate and lactate. Furthermore, salicylate showed both trans-stimulation and cis-inhibition in the urate transport at low and high concentrations, respectively. Finally, coexpression of URAT1 and URATv1 in human kidney epithelial cells was exhibited immunohistochemically. CONCLUSIONS: It is demonstrated that functional cooperation of URAT1 and URATv1 is essential for renal reabsorption of urate, and in the established system influence of drugs on SUA is reflected in the alteration of urate permeability across the renal tubular epithelial cells. SN - 1460-2385 UR - https://www.unboundmedicine.com/medline/citation/23291366/Functional_cooperation_of_URAT1__SLC22A12__and_URATv1__SLC2A9__in_renal_reabsorption_of_urate_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfs574 DB - PRIME DP - Unbound Medicine ER -