Renal tubular and vascular urea transporters: influence of antidiuretic hormone on messenger RNA expression in Brattleboro rats

In the kidney, facilitated urea transport in precise vascular and tubular structures is mainly involved in water conservation. Three urea transporters have been cloned: UT2-long expressed in terminal inner medullary collecting duct (IMCD), UT2-short expressed in thin descending limb, and UT11 in descending vasa recta. The effect of arginine vasopressin (AVP) administration on mRNA expression of these three transporters was examined in Brattleboro rats with diabetes insipidus. V2 effects were discriminated from combined V1 + V2 effects by comparing treatments with 1-deamino-8-D-AVP (dDAVP) (selective V2 agonism) and AVP (V1 and V2 agonism). Acute and chronic treatments were studied. Abundance of specific mRNA was assessed by quantitative Northern blot analysis of RNA extracted from two regions of inner stripe of outer medulla and from two regions of inner medulla (IM). The results show that mRNA of these urea transporters are differently regulated by AVP. (1) Long-term treatment with either AVP or dDAVP does not alter UT2-long mRNA in tip IM (terminal IMCD) except for a transient initial decrease. (2) Unlike AVP, dDAVP induces the appearance of significant expression of UT2-long mRNA in base IM (initial IMCD), indicating a major V2 effect. (3) UT2-short mRNA in deep inner stripe of outer medulla and base IM (thin descending limb of short and long loops, respectively) is progressively upregulated with duration of AVP or dDAVP treatment. (4) The much higher changes in UT2-long and UT2-short induced by dDAVP compared with AVP suggest that they are dependent mainly on V2 agonism, and likely attenuated by V1 agonism. (5) UT11 mRNA expression in tip IM is equally depressed by AVP and dDAVP, indicating that this vascular transporter is also influenced by AVP and/or urine-concentrating activity, via an indirect mechanism that remains to be determined.