The Effect of Age on P-Glycoprotein Expression and Function in the Fischer-344 Rat

We investigated the effect of age on P-glycoprotein (P-gp) expression and function in rat liver, intestine, kidney, and en-dothelial cells of the blood-brain barrier (BBB) and lympho-cytes. Flow cytometric analysis was used to examine P-gp expression in lymphocytes from male Fischer-344 rats from three age groups (young at 3–4 months, intermediate at 13–14 months, and old at 25–26 months). In addition, P-gp function in lymphocytes was assessed by measuring the ability of the P-gp inhibitor verapamil to limit the efflux of the fluorescent P-gp substrate rhodamine 123. P-gp expression was evaluated in the remaining four tissues by Western blot analysis. The effect of age on P-gp expression was tissue-specific. Although lym-phocytic and hepatic P-gp expression increased with age, renal P-gp content was lower in the old kidneys. No statistical dif