Urea restrains aldosterone-induced development of peanut agglutinin-binding on embryonic renal collecting duct epithelia.

Peanut agglutinin (PNA) represents a commonly used marker for beta-type intercalated (IC) cells and their distribution in the corticomedullary course of the collecting duct (CD) in the mature rabbit kidney. It has been shown that aldosterone is able to generate >90% of PNA-binding cells in an embryonic CD epithelium in vitro. In adult kidney, a maximum of only 25% PNA-positive cells is found in the cortical segment of the CD, and PNA-binding completely disappears in the inner-medullary CD. Molecules that regulate the gradual development of CD-specific cells during organ growth are unknown. In the present experiments, it was found that addition of physiologic concentrations of urea to the culture medium is able to restrain the action of aldosterone in embryonic CD epithelia. Urea antagonizes in a concentration-dependent manner the action of aldosterone finally leading to only 10% of PNA-binding cells. The data point to a urea-specific effect, because osmolytes such as NaCl and mannitol did not affect PNA binding. In addition, urea did not influence expression of principal-cell typical markers such as AQP2 and 3. The findings may explain that a higher number of PNA-positive cells is found in the cortical region of the kidney correlated with a low concentration of urea as compared with only few PNA-binding cells in the medullary CD, where a high concentration of urea occurs. Thus, an increasing concentration of urea may trigger the number of PNA-positive cells in the cortical-medullary course of the CD during organ development.