Electrolyte Blood Press.  2007 Dec;5(2):62-67. 10.5049/EBP.2007.5.2.62.

Effects of Increased Uric Acid Intake on the Abundance of Urate-anion exchanger and Organic Anion Transporter Proteins in the Rat Kidney

• Kim S
• Lee CH
• Kang CM
• Kim GH

• KMID: 2052287
• DOI: http://doi.org/10.5049/EBP.2007.5.2.62

Abstract

Renal handling of uric acid mainly occurs in the proximal tubule, and bidirectional transport of urate may involve apical absorption via the urate-anion exchanger (URAT1) and basolateral uptake via organic anion transporters (OAT1 and OAT3). In rat kidneys, we investigated whether the protein abundance of URAT1, OAT1, and OAT3 is affected by the increase in uric acid intake. Male Sprague-Dawley rats were randomly divided into control and uric acid-supplemented groups, and uric acid-supplemented rats were given 0.75 g of uric acid per 180 g body weight per day for 8 days. After the animal experiment, kidneys were harvested and semi-quantitative immunoblotting was carried out from cortical homogenates using polyclonal peptide-derived antibodies to URAT1, OAT1, and OAT3. Serum uric acid level showed an increasing tendency (p=0.055) in the uric acid-supplemented rats (2.60+/- 0.27 mg/dL) compared with control rats (1.97+/-0.29 mg/dL), whereas urinary uric acid excretion was not significantly different between the uric acid-supplemented rats (3.27+/-0.40 mg/d) and control rats (2.61+/-0.34 mg/d). URAT1 protein abundance in cortical homogenates was not significantly different between the uric acid-supplemented rats (132+/-14%) and control rats (100+/-7%). However, OAT1 protein abundance was significantly (p<0.05) increased in the uric acid-supplemented rats (148+/-13%) compared with the control rats (100+/-8%). OAT3 protein abundance was not significantly different between the uric acid-supplemented rats (131+/-12%) and control rats (100+/-17%). In conclusion, OAT1 may have a regulatory role in response to the increase in uric acid intake in the rat kidney. The up-regulation of OAT1 would exert stimulation of urinary uric acid excretion and might contribute to protection from hyperuricemia.

MeSH Terms

Absorption
Animal Experimentation
Animals
Antibodies
Body Weight
Humans
Hyperuricemia
Immunoblotting
Kidney*
Male
Organic Anion Transport Protein 1
Organic Anion Transporters
Rats*
Rats, Sprague-Dawley
Up-Regulation
Uric Acid*
Antibodies
Organic Anion Transport Protein 1
Organic Anion Transporters
Uric Acid

Figure

• 

  Fig. 1 Effect of uric acid supplementation on urate-anion exchanger (URAT1) abundance in rat kidneys. Above: Immunoblot of cortical homogenates from control rats and rats with uric acid supplementation was reacted with anti-URAT1 antibody. Each lane was loaded with a protein sample from a different rat. Below: Densitometric analysis reveals no significant difference in URAT1 protein abundance in rats with uric acid supplementation versus controls.

• 

  Fig. 2 Effect of uric acid supplementation on organic anion transporter type 1 (OAT1) abundance in rat kidneys. Above: Immunoblot of cortical homogenates from control rats and rats with uric acid supplementation was reacted with anti-OAT1 antibody. Each lane was loaded with a protein sample from a different rat. Below: Densitometric analysis reveals a significant increase in OAT1 protein abundance in rats with uric acid supplementation versus controls.

• 

  Fig. 3 Effect of uric acid supplementation on organic anion transporter type 3 (OAT3) abundance in rat kidneys. Above: Immunoblot of cortical homogenates from control rats and rats with uric acid supplementation was reacted with anti-OAT3 antibody. Each lane was loaded with a protein sample from a different rat. Below: Densitometric analysis reveals no significant difference in OAT3 protein abundance in rats with uric acid supplementation versus controls.

• 

  Fig. 4 Effect of uric acid supplementation on aquaporin 1 (AQP1) and aquaporin 2 (AQP2) abundances in rat kidneys. AQP1 and AQP2 immunoblots from cortical homogenates show no signiicant differences in AQP1 and AQP2 protein abundances in rats with uric acid supplementation versus controls, respectively. Each lane was loaded with a protein sample from a different rat.

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