Glucocorticoid and acid-base homeostasis: effects on glutamine metabolism and transport.
The amino acid glutamine serves as a major fuel, powering tubular transport processes and base generation in the kidneys of acidotic animals. Removing the adrenals limits the kidneys' response to an exogenous acid load and impairs the removal rate of glutamine from the blood. Administering glucocorticoid to adrenalectomized (ADX) rats reverses a small net release of glutamine to uptake; similarly, administering an exogenous acid load to ADX rats restores the kidneys to organs of net extraction. Glucocorticoid-induced uptake is substantially less than the filtered glutamine load in contrast to uptake across both the luminal and basolateral surfaces when filtered HCO3- is reduced. Furthermore, mitochondrial glutamine oxidation is glucocorticoid dependent with a distinct impairment exhibited by the ADX acidotic rat kidney. However, combining the effect of reduced filtered HCO3- with glucocorticoid supplementation results in a marked potentiation of glutamine uptake coupled to oxidation. These results are consistent with a proposed proximal tubule cell model in which basolateral glutamine uptake is inversely related to basolateral HCO3- efflux and coupled, in the presence of glucocorticoid, to mitochondrial oxidation. This model of glucocorticoid-induced ammoniagenesis predicts an increased renal work capacity when basolateral transport of a major metabolic fuel, glutamine, is closely coupled to its oxidative metabolism.
Welbourne
T C
TC
Department of Physiology, Louisiana State University Medical Center, Shreveport.
D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D005973:Glutamine / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D010101:Oxygen Consumption; D051381:Rats; D012964:Sodium / Q000494:pharmacology
D001639:Bicarbonates; D005938:Glucocorticoids; D005973:Glutamine; D012964:Sodium