Accumulation of cimetidine by kidney cortex slices

Area of Science:

• Pharmacology
• Nephrology
• Cellular Biology

Background:

• The renal excretion mechanisms for cimetidine, a histamine H2-receptor antagonist, are not fully elucidated.
• Understanding cimetidine's kidney interaction is crucial for optimizing its therapeutic use and managing potential renal effects.

Purpose of the Study:

• To investigate the interaction of cimetidine with dog kidney cortex slices.
• To characterize the transport mechanisms involved in cimetidine accumulation in renal tissue.

Main Methods:

• Utilized 3H-labeled cimetidine in time- and concentration-dependent experiments with dog kidney cortex slices.
• Assessed energy dependence by using cyanide and nitrogen atmosphere incubation.
• Investigated transport mechanisms using inhibitors like cyanine 863, quinine, probenecid, and p-aminohippuric acid.

Main Results:

• Cimetidine was accumulated against a concentration gradient via a saturable, non-metabolic process.
• Uptake demonstrated energy dependence, suggesting active transport.
• Accumulation was inhibited by agents blocking cationic transport (cyanine 863, quinine).
• A probenecid-sensitive component, approximately 20% of uptake, was identified, independent of organic anion transport or general cellular toxicity.

Conclusions:

• Cimetidine renal accumulation primarily occurs through an energy-dependent, saturable active cationic transport system.
• A minor, probenecid-sensitive transport pathway also contributes to cimetidine uptake in the kidney.
• These findings provide insights into the pharmacokinetic handling of cimetidine by the kidney.