Salicylate administered to man in sufficiently large dosage (5 to 6 or more Gm. per day) causes marked uricosuria, characterized by substantially increased urate/inulin clearance ratios attributable to inhibition of tubular reabsorption of the filtered urate. In smaller dosage (1 to 2 Gm. per day) salicylate exerts a contrary effect, retention of urate, associated with lower than normal urate/i...

Human SLC2A9 (GLUT9) is a novel high-capacity urate transporter belonging to the facilitated glucose transporter family. In the present study, heterologous expression in Xenopus oocytes has allowed us to undertake an in-depth radiotracer flux and electrophysiological study of urate transport mediated by both isoforms of SLC2A9 (a and b). Addition of urate to SLC2A9-producing oocytes generated o...

Serum and urinary urate concentrations were studied in 44 patients with homozygous sickle cell (SS) disease, and in 27 controls with normal haemoglobin. Hyperuricaemia (>0.39 mmol/l (6.5 mg/100 ml)) occurred in 41% of SS patients and inversely correlated with renal urate clearance but not with indices of bone marrow turnover. Higher serum urate concentrations occurred in patients with proteinur...

In normal man, the renal clearance of urate is only a small fraction, some 5 to 10 per cent, of the inulin clearance. The prevailing interpretation of this low urate/inulin clearance ratio assumes complete filtrability of the plasma urate at the glomerulus, an assumption supported by several lines of evidence (1-7); reabsorption of 90 to 95 per cent of the filtered urate; and excretion of that ...

Birds are uricotelic and, like humans, maintain high plasma urate concentrations (approximately 300 microM). The majority of their urate waste, as in humans, is eliminated by renal proximal tubular secretion; however, the mechanism of urate transport across the brush-border membrane of the intact proximal tubule epithelium during secretion is uncertain. The dominance of secretory urate transpor...

Plasma urate levels are higher in humans than rodents (240-360 vs. ∼30 μM) because humans lack the liver enzyme uricase. High uricemia in humans may protect against oxidative stress, but hyperuricemia also associates with the metabolic syndrome, and urate and uric acid can crystallize to cause gout and renal dysfunctions. Thus, hyperuricemic animal models to study urate-induced pathologies are ...

Urate is a potent antioxidant at high concentrations but it has also been associated with a wide variety of health risks. Plasma urate concentration is determined by ingestion, production, and urinary excretion; however, factors that regulate urate excretion remain uncertain. The objective of this study was to determine whether cellular stress, which has been shown to affect other renal transpo...

Considerable evidence has shown that elevated plasma or cerebrospinal fluid (CSF) urate levels correlated with a reduced risk of Parkinson's disease (PD). Based on its anti-oxidative properties, urate might serve as one of promising neuroprotective candidates for PD. However, how urate is transported through cell membranes to exert its effects inside the cells in PD is largely unknown. To eluci...

Urate oxidase, or uricase (EC 1.7.3.3), is a peroxisomal enzyme that catalyzes the oxidation of uric acid to allantoin in most mammals. In humans and certain other primates, however, the enzyme has been lost by some unknown mechanism. To identify the molecular basis for this loss, urate oxidase cDNA clones were isolated from pig, mouse, and baboon, and their DNA sequences were determined. The m...

1. When changes in urine flow rate were induced by vasopressin administration in eight subjects, urate excretion decreased by a mean of 14% and was positively correlated with urine flow rate (r = 0.88, P less than 0.01). The effect of vasopressin on urate excretion was not influenced by prior changes in extracellular fluid volume. 2. Mannitol administration in a dose sufficient to prevent vasop...