Project Details


The increased synthesis of ammonia and glucose by the kidney in acidosis is
regulated by both short-term and long-term controls. In the short-term it
is known that increased flux through the pathway in vitro can be brought
about by certain hormones, a decrease in the medium pH or even the addition
of serum from an acidotic animal. The long-term response to acidosis
involves induction of certain key enzymes, phosphoenolpyruvate
carboxykinase, glutaminase and glutamate dehydrogenase. The induction of
phosphoenolpyruvate carboxykinase is known to be due to increased rates of
enzyme synthesis and this correlates with increased amounts of mRNA coding
for the enzyme. The mechanism by which acid-base balance can cause such
changes is unknown. The aim of the work described in this application is
to determine how acidosis can influence the levels of phosphoenolpyruvate
carboxykinase in the kidney. The work will use both rats and chickens
where differences in intracellular enzyme distribution and different
regulatory patterns will allow comparison of mechanisms. The initial work
will characterize the in vivo response to acidosis. Determination of
extracellular signals possibly involved in the acidosis response will be
carried out using isolated proximal tubule cells where changes in the
concentrations of mRNA coding for phosphoenolpyruvate carboxykinase are
readily detectable. Having identified extracellular agents the work will
progress to understanding their intracellular mechanism of action. This
will include experiments to determine if these agents act by changing
transcription rates for the enzyme. The long-term goal is to determine if
a common mechanism is involved in the acid-base mediated changes in the
levels of a number of renal enzymes. In particular the identification of
the "signal" to the kidney during acidosis is of fundamental importance to
the understanding of the regulation of renal metabolism.
Effective start/end date8/1/837/31/86


  • National Institutes of Health


  • Medicine(all)

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