Response of llc-pk1-f+ cells to metabolic acidosis.
Mu, Xinjie, and Tomas Welbourne.
Department of Physiology, LSUMC, Shreveport, LA 71130
APStracts 2:0359C, 1995.
Response of LLC-PK1-F+ cells to metabolic acidosis. Xinjie Mu and T.C.
Welbourne. Am. J. Physiol.: Cell, 1995. The role of extracellular
glutamate formation as opposed to cellular glutamate removal in
regulating monolayer glutamate content in response to metabolic
acidosis was studied in LLC-PK1-F+ cells. Exposure to metabolic
acidosis, 14mM bicarbonate and pH 7.1, for 18h resulted in a 24% fall
in monolayer glutamate content. Of this, approximately half could be
attributed to enhanced glutamate removal via glutamate dehydrogenase
consistent with a rise in ammonium production. The remainder appears
due to reduced extracellular glutamate formation as a consequence of
diminished gamma glutamyltranspeptidase, r-Gt, activity. Metabolic
acidosis, but not respiratory acidosis, resulted in a 33% fall in r
-Gt activity and a proportional fall in extracellular glutamate
formation; glutamate transport into these cells was not rate-limiting
in acidosis. Overall glutamine utilization decreased 36%, reflecting
the fall in r-Gt activity as well as a decrease in a pH sensitive
glutamine uptake while glutamine transport coupled to the PDG flux
increased. Noteworthy, the increased ammonium produced in metabolic
acidosis was preferentially secreted into the apical compartment;
acid secretion, but not production, was similarly increased. Thus
reduced cellular glutamate appears to coordinate activation of
intracellular glutaminase to the apical membrane Na+/H+/NH4+
exchanger consistent with the functioning kidney response to
metabolic acidosis.
Received 15 May 1995; accepted in final form 11 September 1995.
APS Manuscript Number C271-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95