Urate-2-14C transport in the rat nephron
The Journal of Clinical Investigation
|January 1, 1971
Summary
This study reveals that urate reabsorption occurs primarily in the proximal tubules of rat kidneys, suggesting a carrier-mediated transport mechanism. Drug treatments affecting urate transport primarily impact this proximal reabsorption.
Area of Science:
- Nephrology
- Renal Physiology
- Urate Transport
Background:
- Understanding intrarenal urate transport is crucial for managing conditions like gout and kidney stones.
- Previous studies suggest complex reabsorption and secretion processes for urate within the nephron.
Purpose of the Study:
- To investigate the localization and kinetics of urate transport in the rat kidney using microinjections.
- To examine the effects of specific drugs on urate reabsorption in different segments of the nephron.
Main Methods:
- Microinjection of urate-2-(14)C and inulin-3H into proximal and distal tubules of anesthetized rats.
- Serial collection of ureteral urine to determine urate recovery rates.
- Administration of drugs (probenecid, pyrazinoate, PAH) and varying urate concentrations to assess transport mechanisms.
Main Results:
- Urate recovery increased significantly with more distal injection sites, indicating reduced reabsorption along the tubule.
- Probenecid, pyrazinoate, and PAH enhanced urate recovery after proximal injections, suggesting inhibition of proximal reabsorption.
- High urate concentrations demonstrated saturation kinetics, supporting a carrier-mediated transport system.
- Delayed urate recovery was unaffected by drug administration or injection site.
Conclusions:
- Urate reabsorption is predominantly localized to the proximal tubule in rats.
- A carrier-mediated transport system for urate is likely present at the luminal membrane of proximal tubular cells.
- The studied drugs appear to inhibit urate reabsorption at the proximal site, likely via luminal membrane interactions.
Related Concept Videos
01:15Drug Elimination by Renal Route: Tubular Secretion
Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
01:28Tubular Reabsorption and Secretion
Tubular secretion and reabsorption are two critical processes in the nephron tubule of the kidneys. When the fluid filtered from the glomerulus enters the proximal convoluted tubule, it is referred to as filtrate, and its composition changes due to tubular reabsorption and secretion.
Tubular reabsorption is a selective process that starts when the filtrate enters the proximal tubules. It involves substances traveling through the transcellular route (through the tubule cell and peritubular...
Tubular reabsorption is a selective process that starts when the filtrate enters the proximal tubules. It involves substances traveling through the transcellular route (through the tubule cell and peritubular...
01:28Reabsorption and Secretion in the PCT
The Proximal Convoluted Tubule, or PCT, plays a pivotal role in the body's filtration system. They are primarily responsible for reabsorbing solutes and water from the filtered fluid produced by the glomeruli. Most of the filtered water, ions, and organic solutes such as glucose and amino acids are reabsorbed by the PCT.
Transport mechanisms involving sodium ions (Na+) contribute significantly to solute reabsorption. These mechanisms include symport and antiport processes.
A key example is the...
Transport mechanisms involving sodium ions (Na+) contribute significantly to solute reabsorption. These mechanisms include symport and antiport processes.
A key example is the...
01:17Reabsorption and Secretion in the Loop of Henle
The thick ascending limb of the nephron loop has Na+–K+–2Cl− symporters in the apical membranes of its cells. These symporters simultaneously reclaim one sodium ion, one potassium ion, and two chloride ions from the tubular fluid. Sodium ions are actively transported into the interstitial fluid at the base and sides of the cell, diffusing into the vasa recta. Chloride ions move through leakage channels in the basolateral membrane into the interstitial fluid and then into the vasa recta.
01:28Renal Drug Excretion: Tubular Secretion
Active tubular secretion is a robust, energy-demanding process that utilizes carrier systems to transport drugs into renal tubules. The active renal secretion systems include the organic anion transporter (OAT) for weak acids and the organic cation transporter (OCT) for weak bases. Structurally similar drugs can compete for the same transporter, potentially leading to drug accumulation and toxicity. However, this principle can be exploited therapeutically. One example is probenecid (Probalan),...
01:22Physiology of the Genitourinary System II: Tubular Reabsorption and Secretion
The kidneys maintain homeostasis through filtration, reabsorption, and secretion. Tubular reabsorption and secretion are crucial in forming urine and regulating electrolytes, water balance, and waste elimination.Tubular Reabsorption and Secretion ProcessesTubular reabsorption is the process that reclaims essential substances such as electrolytes, glucose, amino acids, and water from the glomerular filtrate back into the bloodstream. This is achieved through passive and active transport...