Gender differences in the renal handling on drugs and toxins have received too little attention. In the present study, a variety of preparations were used to examine the basis for the greater effectiveness of the male kidneys in the elimination of p-aminohippurate (PAH) in rats. Renal clearance of PAH was significantly lower in female rats as consequence of its smaller filtered and secreted load. The gender difference in the filtered load may be accounted for the lower value of glomerular filtration rate (GFR) displayed by female rats as compared with males. The lower value of the renal blood flow observed in females might explain, at least in part, the decrease in the GFR and in the secreted load of PAH. In females, maximal uptake for PAH transport into renal basolateral membrane vesicles decreased to 52+/-9% (P < 0.05) and Michaelis-Menten constant for PAH uptake into renal brush border membrane vesicles was increased to 163+/-8% (P < 0.05). These changes might also explain the lower secreted load of PAH. The sex difference in the renal clearance of PAH was also evidenced by the reduced systemic clearance observed in female rats.

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Sex differences in the kinetic parameters of p-aminohippuric acid (PAH) transport in brush border (BBMV) and basolateral (BLMV) membrane vesicles from kidney cortex have been observed. Membrane fluidity of BBMV was higher in females as compared with male rats as indicated by anisotropy values (0.1897 +/- 0.0010 vs. 0.2003 +/- 0.0014, p < 0.05, for females and males respectively). Membrane fluidity of BLMV were similar in both sexes. Western blot studies revealed that OAT1 protein in female BLMV was present at only 40% of level found in BLMV from male rats. The lower expression of OAT1 in BLMV in association with the higher BBMV fluidity (which may affect the affinity of PAH transporter in this membrane domain) observed in females may be responsible, at least in part, for the gender difference described in renal PAH secretion.