ONTOGENY OF RABBIT RENAL CORTICAL NHE3 AND NHE1 - EFFECT OF GLUCOCORTICOIDS

The neonatal proximal tubule has a lower rate of bicarbonate absorptio n and Na+/H+ antiporter activity than the proximal tubule of adult ani mals, Two isoforms of the Na+/H+ antiporter have been localized to the proximal tubule. NHE3 is located on the apical membrane, whereas NHE1 , the isoform found on most mammalian cells, is present on the basolat eral membrane. The Na+/H+ antiporter isoforms that increase with renal maturation are unknown. The purpose of the present study was to exami ne the maturation of rabbit renal cortical NHE3 and NHE1 mRNA and prot ein abundance and to determine whether the rate of maturation of these isoforms was affected by glucocorticoids. Renal cortex from neonatal rabbits (1 wk) had approximately one-fourth the NHE3 mRNA and protein abundance as that from adult animals. Renal cortical NHE1 mRNA and pro tein abundance did not change significantly during maturation. Glucoco rticoids have been shown to accelerate the maturation of neonatal bica rbonate absorption and apical membrane Na+/H+ antiporter activity. Dai ly subcutaneous administration of dexamethasone starting at 4 days of age (10 mu g/100 g body wt) for 3 days and 2 h before being killed res ulted in a twofold increase in NHE3 mRNA abundance and a threefold inc rease in NHE3 protein abundance. NHE1 mRNA and protein abundance were unaffected. These data show that there is selective maturation of NHE3 during renal cortical development, which can be accelerated by admini stration of glucocorticoids.