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Title: Renal transport of bisphosphonates: accumulation by renal cortical slices enhanced by calcium phosphate ions

Abstract

Bisphosphonates have been recognized as useful therapeutic agents in metabolic bone disease. Earlier studies showed a net renal secretion of 1-hydroxy-ethylidene-1,1-bisphosphonate (HEBP). They suggested a renal cellular uptake of this compound. The authors further studied this concept by investigating the uptake in vitro of /sup 14/C-HEBP by rat renal cortex slices. HEBP was accumulated against a concentration gradient, a process that was dependent on time, temperature, and substrate concentration. Unlike that of /sup 3/H-p-aminohippurate, the uptake was not affected by change in medium Na+ or glucose and acetate concentration, or by anoxia and various metabolic inhibitors. It was, however, markedly increased by raising the medium calcium and inorganic phosphate concentration. Equilibrium dialysis with renal cortex homogenates suggests that HEBP binds to a cytosolic macromolecule through a process that exhibits saturability and calcium dependency. In conclusion, the results suggest that the bisphosphonate HEBP can penetrate kidney cells by a process that does not appear to be energy dependent, but is markedly influenced by the extracellular calcium-phosphate concentration.

Authors:
; ;
Publication Date:
Research Org.:
Univ. of Bern, Switzerland
OSTI Identifier:
5247045
Resource Type:
Journal Article
Journal Name:
J. Lab. Clin. Med.; (United States)
Additional Journal Information:
Journal Volume: 1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; PHOSPHONATES; MEMBRANE TRANSPORT; ACETATES; ANOXIA; CALCIUM; CARBON 14 COMPOUNDS; CATIONS; CHEMICAL BONDS; GLUCOSE; IN VITRO; KIDNEYS; PHOSPHATES; RATS; SKELETAL DISEASES; SODIUM COMPOUNDS; TEMPERATURE DEPENDENCE; TRITIUM COMPOUNDS; UPTAKE; ALDEHYDES; ALKALI METAL COMPOUNDS; ALKALINE EARTH METALS; ANIMALS; BODY; CARBOHYDRATES; CARBOXYLIC ACID SALTS; CHARGED PARTICLES; DISEASES; ELEMENTS; HEXOSES; IONS; LABELLED COMPOUNDS; MAMMALS; METALS; MONOSACCHARIDES; ORGANIC COMPOUNDS; ORGANIC PHOSPHORUS COMPOUNDS; ORGANS; OXYGEN COMPOUNDS; PHOSPHORUS COMPOUNDS; RODENTS; SACCHARIDES; VERTEBRATES; 550501* - Metabolism- Tracer Techniques

Citation Formats

Troehler, U, Bonjour, J P, and Fleisch, H. Renal transport of bisphosphonates: accumulation by renal cortical slices enhanced by calcium phosphate ions. United States: N. p., 1985. Web.
Troehler, U, Bonjour, J P, & Fleisch, H. Renal transport of bisphosphonates: accumulation by renal cortical slices enhanced by calcium phosphate ions. United States.
Troehler, U, Bonjour, J P, and Fleisch, H. Mon . "Renal transport of bisphosphonates: accumulation by renal cortical slices enhanced by calcium phosphate ions". United States.
@article{osti_5247045,
title = {Renal transport of bisphosphonates: accumulation by renal cortical slices enhanced by calcium phosphate ions},
author = {Troehler, U and Bonjour, J P and Fleisch, H},
abstractNote = {Bisphosphonates have been recognized as useful therapeutic agents in metabolic bone disease. Earlier studies showed a net renal secretion of 1-hydroxy-ethylidene-1,1-bisphosphonate (HEBP). They suggested a renal cellular uptake of this compound. The authors further studied this concept by investigating the uptake in vitro of /sup 14/C-HEBP by rat renal cortex slices. HEBP was accumulated against a concentration gradient, a process that was dependent on time, temperature, and substrate concentration. Unlike that of /sup 3/H-p-aminohippurate, the uptake was not affected by change in medium Na+ or glucose and acetate concentration, or by anoxia and various metabolic inhibitors. It was, however, markedly increased by raising the medium calcium and inorganic phosphate concentration. Equilibrium dialysis with renal cortex homogenates suggests that HEBP binds to a cytosolic macromolecule through a process that exhibits saturability and calcium dependency. In conclusion, the results suggest that the bisphosphonate HEBP can penetrate kidney cells by a process that does not appear to be energy dependent, but is markedly influenced by the extracellular calcium-phosphate concentration.},
doi = {},
journal = {J. Lab. Clin. Med.; (United States)},
number = ,
volume = 1,
place = {United States},
year = {1985},
month = {7}
}