AJP - Renal Physiology, Vol 251, Issue 3 547-F561, Copyright © 1986 by American Physiological Society
Renal tissue citrate: independence from citrate utilization, reabsorption, and pH
N. H. Anaizi, J. J. Cohen, A. J. Black and S. J. Wertheim
During alkalosis in vivo, renal tissue [citrate] [( citrate]t) increases
and citrate reabsorption (Tcit) and utilization (Qcit) simultaneously
decrease. The decrease in Qcit is interpreted to cause the increased
[citrate]t, which in turn decreases Tcit X Renal citrate handling and
[citrate]t could be regulated by other mechanisms, since alkalosis changes
[substrate] and [H+] in extracellular (ECF) and intracellular (ICF) fluid.
Also, since high plasma [citrate] decreases ionized [Ca2+] (Cai), it is not
possible to determine in vivo whether there is a maximum for Tcit or Qcit
and whether change in extracellular fluid (delta ECF) pH affects these
maxima. We perfused the substrate-limited isolated rat kidney for either
110 (n = 36) or 50 min (n = 44) at pH 7.2, 7.4, or 7.6; pH was changed by
varying [HCO3-]; Cai was held constant at approximately 2.5 meq/liter. When
citrate was the only substrate available in a Krebs-Ringer-HCO3 perfusate
containing 6% substrate-free albumin, both Qcit and Tcit had maximal rates:
Qcit much greater than Tcit; at pH 7.6, Qcit and Tcit were significantly
reduced below their values at pH 7.2 or 7.4. In contrast to in vivo
observations, [citrate]t was not significantly increased at high ECF pH. To
test whether [citrate]t in the perfused kidney can increase in alkalosis,
11 additional perfusions were done in the presence of glucose plus lactate
plus malate but without added citrate: [citrate]t = 0.6 mumol X g-1 at pH
7.6 and 0.3 mumol X g-1 at pH 7.2 (P less than 0.01); no citrate was
detectable in the perfusate, and urinary citrate excretion was negligible.
Thus, in the isolated rat kidney, an increase in [citrate]t occurred in
alkalosis and was derived from precursors and not from citrate in the ECF.
Overall, when only citrate was available to the isolated kidney during
alkalosis, a significant rise in [citrate]t did not occur, although Vmax
for Tcit and Qcit decreased. These effects of alkalosis on Tcit are
consistent with observations in brush-border vesicles, where divalent
citrate is the preferential substrate for luminal Na+-coupled transport; by
contrast, high ECF pH and [HCO-3] apparently decrease Qcit by a direct
effect on the utilization of citrate.
