Project: Research project

Grant Details


The long-term objectives of this Program Project are to understand- 1)
the mechanisms involved in renal tubular transport of organic cations (or
bases), 2) the mechanisms involved in renal tubular transport of organic
anions (or acids), particularly the transport of uric acid in relation to
stone formation; 3) the regulation of physiologically and
pharmacologically important molecules transported by these pathways; 4)
the possible toxic effects of molecules transported by these pathways;
and 5) the processes by which renal toxicants interfere with these
pathways. The research strategy involves an integrated approach among
four individual projects using systems that represent different levels of
biological organization -- from the whole animal to the cell membrane --
and using a wide variety of techniques. Several species (or tissue from
several species) of mammalian--rabbit, rat, and pig and nonmammalian--
snake and chicken -- species will be employed to take advantage of
exaggerated function or ease of preparation in different species.
Specific preparations, reflecting levels of biological organization, to
be used are whole animals (Projects #2 and #4), kidney slices (Project
#3), isolated renal tubules (Projects 01, *2, *3, and *4), renal cells in
culture (Projects *2 and *3), and renal membrane vesicles (Projects 01,
02, and 04). Major techniques or experimental designs linking the
projects include: clearance studies (Projects #2 and *4); radiotracer
studies of transport (Projects *I, *2, *3, and #4); histological,
histochemical, and ultrastructural analyses of transport or toxicity
(Projects 03 and 04); measurements of intracellular concentrations of
organic ions by isotopic labeling techniques (Projects *1, *2, and *3)
and of intracellular activities by ion-selective microelectrodes
(Projects *1 and *2); optical procedures for measuring transport and
intracellular pH and pCa (Projects *I, *2, and *3); and the use of
compounds with different chemical structures for probing the specificity
and chemical structure of the carriers and for isolating and identifying
them (Projects *1 and *2) or for probing specificity of toxic effects
(Projects 01, 02, and *3).
Effective start/end date8/1/897/31/95


  • National Institutes of Health: $456,378.00
  • National Institutes of Health: $468,600.00
  • National Institutes of Health: $498,564.00


  • Medicine(all)


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