Tags

Type your tag names separated by a space and hit enter

[Human renal urate transpoter URAT1 mediates the transport of salicylate].
Nihon Jinzo Gakkai Shi. 2010; 52(4):499-504.NJ

Abstract

Salicylic acid derivatives are the most prescribed analgesic-antipyretic and anti-inflammatory agents. It is well known that salicylate has a paradoxical effect on renal urate excretion. At low doses (5 - 10 mg/dL serum), renal urate excretion is decreased, whereas at high doses (> 15 mg/dL serum), renal urate excretion is increased. Since the molecular identification of the renal apical urate/anion exchanger URAT1, it has been suggested that this protein is responsible for the paradoxical effect because of cis-inhibition of salicylate (1 mM) on urate uptake by URAT1-expressing oocytes. The purpose of this study was to examine whether or not URAT1 is responsible for the paradoxical effect of salicylate. In URAT1-stably expressing HEK293 (HEK293-URAT1) cells, salicylate inhibited [14C] urate uptake dose-dependently (IC50, 23.9 microM). URAT1 mediated the time-dependent uptake of [3H] salicylate in these cells. [3H] Salicylate uptake via URAT1 was inhibited by non-labelled urate and salicylate, and the uricosuric agent, benzbromarone. In the URAT1-expressing oocytes, we observed the time- and concentration-dependent transport of salicylate (Km : 25.3 microM). Moreover, non-labelled salicylate injected into the URATI-expressing oocytes stimulated [14C] urate uptake. These results suggest that the "paradoxical effect" of salicylate can be explained by two modes of salicylate interaction with URAT1 : (1) acting as an exchange substrate to facilitate urate reabsorption, and (2) acting as an inhibitor for urate reabsorption.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

jpn

PubMed ID

20560471

Citation

Ohtsu, Naoko, et al. "[Human Renal Urate Transpoter URAT1 Mediates the Transport of Salicylate]." Nihon Jinzo Gakkai Shi, vol. 52, no. 4, 2010, pp. 499-504.
Ohtsu N, Anzai N, Fukutomi T, et al. [Human renal urate transpoter URAT1 mediates the transport of salicylate]. Nihon Jinzo Gakkai Shi. 2010;52(4):499-504.
Ohtsu, N., Anzai, N., Fukutomi, T., Kimura, T., Sakurai, H., & Endou, H. (2010). [Human renal urate transpoter URAT1 mediates the transport of salicylate]. Nihon Jinzo Gakkai Shi, 52(4), 499-504.
Ohtsu N, et al. [Human Renal Urate Transpoter URAT1 Mediates the Transport of Salicylate]. Nihon Jinzo Gakkai Shi. 2010;52(4):499-504. PubMed PMID: 20560471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Human renal urate transpoter URAT1 mediates the transport of salicylate]. AU - Ohtsu,Naoko, AU - Anzai,Naohiko, AU - Fukutomi,Toshiyuki, AU - Kimura,Toru, AU - Sakurai,Hiroyuki, AU - Endou,Hitoshi, PY - 2010/6/22/entrez PY - 2010/6/22/pubmed PY - 2010/8/4/medline SP - 499 EP - 504 JF - Nihon Jinzo Gakkai shi JO - Nihon Jinzo Gakkai Shi VL - 52 IS - 4 N2 - Salicylic acid derivatives are the most prescribed analgesic-antipyretic and anti-inflammatory agents. It is well known that salicylate has a paradoxical effect on renal urate excretion. At low doses (5 - 10 mg/dL serum), renal urate excretion is decreased, whereas at high doses (> 15 mg/dL serum), renal urate excretion is increased. Since the molecular identification of the renal apical urate/anion exchanger URAT1, it has been suggested that this protein is responsible for the paradoxical effect because of cis-inhibition of salicylate (1 mM) on urate uptake by URAT1-expressing oocytes. The purpose of this study was to examine whether or not URAT1 is responsible for the paradoxical effect of salicylate. In URAT1-stably expressing HEK293 (HEK293-URAT1) cells, salicylate inhibited [14C] urate uptake dose-dependently (IC50, 23.9 microM). URAT1 mediated the time-dependent uptake of [3H] salicylate in these cells. [3H] Salicylate uptake via URAT1 was inhibited by non-labelled urate and salicylate, and the uricosuric agent, benzbromarone. In the URAT1-expressing oocytes, we observed the time- and concentration-dependent transport of salicylate (Km : 25.3 microM). Moreover, non-labelled salicylate injected into the URATI-expressing oocytes stimulated [14C] urate uptake. These results suggest that the "paradoxical effect" of salicylate can be explained by two modes of salicylate interaction with URAT1 : (1) acting as an exchange substrate to facilitate urate reabsorption, and (2) acting as an inhibitor for urate reabsorption. SN - 0385-2385 UR - https://www.unboundmedicine.com/medline/citation/20560471/[Human_renal_urate_transpoter_URAT1_mediates_the_transport_of_salicylate]_ DB - PRIME DP - Unbound Medicine ER -