Distribution of major organic osmolytes in rabbit kidneys in diuresis and antidiuresis

Sorbitol, glycerophosphorylcholine (GPC), inositol, and betaine are organic osmolytes that accumulate in renal medullary cells. Two roles have been proposed for them: 1) that all four are "compatible osmolytes" that help regulate cell volume without disturbing function, and 2) that the methylamines (GPC and betaine) are "counteracting osmolytes," i.e., stabilizers that offset the perturbing effects of the high urea concentration. To test these hypotheses we have measured the osmolyte gradients in diuresis and antidiuresis in rabbit kidneys cut in 7 sections along the corticopapillary axis. In both antidiuresis and diuresis, inositol was highest in the outer medulla and decreased toward the tip of the inner medulla. In antidiuresis, contents of sodium, urea, sorbitol, GPC, and betaine increased monotonically toward the tip of the inner medulla. All osmolytes were significantly lower in diuresis compared with antidiuresis in two or more kidney sections. Urea, GPC, and sorbitol had the greatest differences between the two states. The sum of the four (mainly intracellular) compatible osmolytes showed a strong linear correlation with Na (presumably mostly extracellular), with a similar slope in both states, consistent with the compatible osmolytes hypothesis. Considering the osmolytes individually, only two linear correlations were highly significant and had similar slopes in both diuresis and antidiuresis: betaine with Na and GPC with urea. The latter is consistent with the counteracting osmolytes hypothesis, suggesting that GPC is the main agent stabilizing against urea in the renal medulla.