Renal Ontogeny of P-Glycoprotein/MDR1 in Rat

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Renal Ontogeny of P-Glycoprotein/MDR1 in Rat

BACKGROUND: P-glycoprotein (Pgp/MDR1) is an ATP-dependent, integral plasma-membrane efflux pump that is constitutively expressed on adult apical brush-border epithelium of renal proximal tubules. This Pgp/MDR1 tissue distribution and localization affects the absorption, distribution, metabolism, and excretion of Pgp/MDR1 substrates. The ontogeny of rat Pgp/MDR1 is still doubtful, and such knowledge may be helpful in understanding age-related pharmacokinetics. The purpose of this study was to determine, whether Pgp/MDR1 expression is altered during development.

METHODS: Postnatal expression of Pgp was determined using immunohistochemical method. Tissue from Wistar rat were isolated on the 1st day (D1), 7th day (D7), 14th day (D14), 21st day of life (D21) and from adult animals (60 days old; Ad).

RESULTS: Our ontogeny study illustrated that expression of Pgp was relatively constant from birth to adulthood.

CONCLUSIONS: Knowledge of the ontogeny of transport proteins involved in distribution and elimination of drugs is important for adequate interpretation of the results of toxicity studies in juvenile animals.

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