Moment analysis of drug disposition in rat kidney: Role of basolateral membrane transport in renal transepithelial transport of p-aminohippurate

Y. Saito, Yusuke Tanigawara, N. Okamura, H. Shimizu, A. Kamiya, R. Hori

Research output: Contribution to journalArticle

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Abstract

The determining step in transepithelial transport of p-aminohippurate (PAH) in renal tubular secretion has been elucidated in the rat isolated perfused kidney. The method was based upon a multiple indicator dilution experiment and non-compartmental moment analysis. Single-pass dilution curves were obtained from venous and urinary effluents after simultaneous intra-arterial injections of Evans blue with albumin, [3H]inulin and [14C]PAH. Probenecid was used as a transport inhibitor and dissolved in both perfusate and injection solution. The urinary excretion of PAH decreased depending on the probenecid concentration, while that of inulin was not affected. No correlation was observed between the amount of secretion and the mean residence time of secreted PAH in renal epithelial cells [T̄(cell)]. Since T̄(cell) ought to be affected by the rate of secretion from cells to lumen, it was suggested that the secretion rate was independent of the amount secreted. In contrast, the amount of PAH excreted via tubular secretion showed a linear correlation with the volume of distribution in the kidney and the apparent rate constant for tubular uptake of PAH. Since these kinetic parameters reflect the transport from blood into cells across the basolateral membranes of renal epithelial cells, the present results demonstrated that basolateral membrane transport is a determining step in the transcellular transport of PAH and that the major effect of probenecid is the inhibition of transport from blood into cells.

Original languageEnglish
Pages (from-to)311-316
Number of pages6
JournalJournal of Pharmacy and Pharmacology
Volume43
Issue number5
Publication statusPublished - 1991
Externally publishedYes

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p-Aminohippuric Acid
Kidney
Membranes
Probenecid
Pharmaceutical Preparations
Inulin
Blood Cells
Epithelial Cells
Intra-Arterial Injections
Transcytosis
Evans Blue
Albumins
T-Lymphocytes
Injections

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology

Cite this

Moment analysis of drug disposition in rat kidney : Role of basolateral membrane transport in renal transepithelial transport of p-aminohippurate. / Saito, Y.; Tanigawara, Yusuke; Okamura, N.; Shimizu, H.; Kamiya, A.; Hori, R.

In: Journal of Pharmacy and Pharmacology, Vol. 43, No. 5, 1991, p. 311-316.

Research output: Contribution to journalArticle

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