Hormonal and Na+ effect on renal glutamine uptake.
The flux of glutamine through cellular PDG or extracellular gamma-glutamyltransferase may reflect competition between the membrane glutamine transporter and extracellular hydrolysis. To test this model, kidneys from nonacidotic (NA) and chronically acidotic rats were isolated and perfused with glutamine in a Na+ media and then with a media in which choline replaced Na+. Replacing Na+ abolished the Na+ gradient and completely eliminated the transport of filtered glutamine back into the perfusate. Nevertheless NH4+ production and glutamine utilization remained intact while glutamate accumulated in the extracellular compartments. In the Na+ media, acidotic rat kidneys produced 2.6 times more NH4+ and utilized 1.5-fold more glutamine than their NA counterparts. In the choline media, acidotic rat kidneys had a large drop in NH4+ production but not in glutamine utilization; associated with this was a large glutamate accumulation in the extracellular compartments consistent with flow through the extracellular pathway. To demonstrate the applicability of this model, the role of the adrenals and glucocorticoids in modulating fluxes over these pathways was studied. Kidneys from adrenalectomized acidotic rats exhibited a diminished transport of glutamine, reduced utilization and decreased ammoniagenesis; glutamate accumulation in the extracellular compartment rose consistent with greater flux via the extracellular glutaminase. Supplementing these animals with triamcinolone restored flow into the cellular pathway. The results confirm the in situ activity of two renal glutaminases whose relative contributions to renal ammoniagenesis are dependent on the acid base balance, glucocorticoids, and the existing Na+ gradient.
Welbourne
T C
TC
Department of Physiology and Biophysics, Louisiana State Medical Center, Shreveport 71130.
D000138:Acidosis / Q000378:metabolism; D000315:Adrenalectomy; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002794:Choline / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012964:Sodium / Q000494:pharmacology*; D014221:Triamcinolone / Q000494:pharmacology
D005971:Glutamates; D000643:Ammonium Chloride; D005973:Glutamine; D014221:Triamcinolone; D012964:Sodium; D002794:Choline