Long-term regulation of four renal aquaporins in rats

Abstract

The aquaporins are molecular water channels expressed in the kidney and other organs. To investigate long-term regulation of renal expression of these water channels, we carried out immunoblotting studies using membrane fractions from rat renal cortex and medulla. Both 48-h water restriction in Sprague-Dawley rats and 5-day arginine vasopressin (AVP) infusion in Brattleboro rats caused significant increases in the expression levels of two aquaporins, aquaporin-2 and aquaporin-3, while the levels of aquaporin-1 and aquaporin-4 were unchanged. The increases in aquaporin-2 and aquaporin-3 expression were seen in inner and outer medulla as well as cortex. Ablation of the corticomedullary interstitial osmotic gradient with an infusion of furosemide did not eliminate the upregulatory response to AVP infusion in Brattleboro rats. Furthermore, 5-day furosemide infusion to Sprague-Dawley rats did not decrease expression levels of the collecting duct aquaporins, but rather increased them. We conclude that the expression of aquaporin-2 and aquaporin-3, but not aquaporin-1 or aquaporin-4, is increased in response to elevated circulating AVP. Because regulation of aquaporin-2 and aquaporin-3 levels was observed in the cortex and because osmotic gradient ablation did not abrogate the increase, we conclude that changes in interstitial osmolality are not necessary for the AVP-induced upregulation of aquaporin-2 and aquaporin-3 expression.

Aquaporin-2 and urea transporter-A1 are up-regulated in rats with Type I diabetes mellitus

“…In fact, they are different. In the case of UT-A1, chronic dDAVP infusion did not induce a change in mRNA and protein expression in whole IM [31,37] in contrast to the considerable increase seen in diabetes mellitus (present study). A recent study showed that chronic dDAVP infusion induced a shift of UT-A1 protein from the tip to the base of IM [38].…”

“…The 117000 M r protein was greatly increased in both IM base and tip and thus in both initial and terminal IMCD. Such an increase in the 117000 M r band has been reported for total inner medulla in several cases of high urine flow rate (furosemide treatment, Brattleboro rats with diabetes insipidus, low protein diet [31]). …”

“…The 97000 M r protein was not changed in the IM base and greatly underexpressed in IM tip, as has already observed 3 days after streptozotocin injection [25]. It is noteworthy that, among a number of situations in which urinary concentrating activity is altered (alterations in protein or water intake, AVP or dDAVP (V2 agonist) infusion, furosemide treatment [31]), diabetes mellitus is the only one that exhibits a change in the 97000 M r protein. The 117000 M r protein was greatly increased in both IM base and tip and thus in both initial and terminal IMCD.…”

“…Each column represents the mean of 4±5 rats per group. No significant difference was found between DM and CO rat mellitus is different because the changes in UT mRNA and protein abundance observed in diabetes mellitus differ from those resulting from protein-rich diet (unchanged mRNA [40], and decreased 117000 M r isoform [31]). In contrast, some of the diabetes-induced changes resemble those induced by chronic low protein feeding, such as extension of UT-A1 mRNA [41] and vasopressin-dependent urea permeability [33,42] to the initial part of the IMCD, increase in the 117000 M r isoform [31], and lack of change in UT-A2 and UT-B1 mRNA abundance [40].…”

“…This could be responsible for a greater transport capacity because, in situations in which the 117000 M r protein was also shown to be upregulated (water loading, furosemide-induced diuresis, and low protein diet) [31], the basal and vasopressin-stimulated urea permeabilities were also increased [32,33]. Therefore, in diabetes, the increase in UT-A1 117000 M r protein should improve urea reabsorption along the entire IMCD, thereby improving too medullary hypertonicity.…”