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 tubu lar structures is mainly involved in water conservation. Three urea tr ansporters have been cloned: UT2-long expressed in terminal inner medu llary collecting duct (IMCD), UT2-short expressed in thin descending l imb, and UT11 in descending vasa recta. The effect of arginine vasopre ssin (AVP) administration on mRNA expression oi these three transporte rs was examined in Brattleboro rats with diabetes insipidus. V2 effect s were discriminated from combined V1 + V2 effects by comparing treatm ents 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-te rm treatment with either AVP or dDAVP does not alter UT2-long mRNA in tip IM (terminal IMCD) except for a transient initial decrease. (2) Un like AVP, dDAVP induces the appearance of significant expression of UT 2-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 (t hin descending limb of short and long loops, respectively) is progress ively upregulated with duration of AVP or dDAVP treatment. (4) The muc h higher changes in UT2-long and UT2-short induced by dDAVP compared w ith AVP suggest that they are dependent mainly on V2 agonism, and like ly attenuated by V1 agonism. (5) UT11 mRNA expression in tip IM is equ ally depressed by AVP and dDAVP, indicating that this vascular transpo rter is also influenced by AVP and/or urine-concentrating activity, vi a an indirect mechanism that remains to be determined.