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Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II

Nephrology Section 111L, Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, and The David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California

Submitted 14 July 2008 ; accepted in final form 20 October 2008

The proximal tubule defends the body against acid challenges by enhancing its production and secretion of ammonia. Our previous studies demonstrated an enhanced ammoniagenic response of the proximal tubule to ANG II added to the lumen in vitro after an in vivo acid challenge. The present study examined the effect of NH₄Cl acid loading in vivo on renal cortical type 1 ANG II (AT₁) receptor expression, the effect of low pH on AT₁ receptor expression in a proximal tubule cells in culture, and their response to ANG II. A short-term (18 h) NH₄Cl load in vivo resulted in increased renal cortical AT₁ receptor mRNA expression and increased brush-border membrane AT₁ receptor protein expression levels. Changing the cell culture pH from 7.4 to 7.0 for at least 2 h increased cell surface expression of AT₁ receptors and enhanced the stimulatory effect of ANG II on ammonia production rates. This increased ammoniagenic response to ANG II and the early enhancement of cell surface expression induced by exposure of the cultured proximal tubule cells to pH 7.0 were prevented by treatment with colchicine. These results suggest that, after acid challenges, the enhanced ammoniagenic response of the proximal tubule to ANG II is, in part, mediated by increased AT₁ receptor cell surface expression and that the enhancement of receptor expression plays an important role in the early response of the proximal tubule to acid challenges.

ammoniagenesis; angiotensin type receptor; cell surface; acidosis; colchicine

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