Vol. 291, Issue 2, 920-923, November 1999

Regulation of Aquaporin-2 Expression by the ₂-Adrenoceptor Agonist Clonidine in the Rat¹

Asad Junaid , Li Cui, S. Brian Penner and Donald D. Smyth

Departments of Internal Medicine (A.J., B.P.) and Pharmacology and Therapeutics (B.P., D.D.S.), Faculty of Medicine, St. Boniface Research Centre (A.J., L.C.), University of Manitoba, Winnipeg, Manitoba, Canada

Aquaporin-2 (AQP-2), the major water channel responsible for water balance, has been shown to be regulated by the binding of vasopressin to V₂ vasopressin receptors in the medullary collecting duct. ₂-Adrenoceptor agonists such as clonidine have been associated with an increase in free water clearance that was secondary to an inhibition of the ability of vasopressin to increase cAMP levels in the collecting ducts. This investigation focused on the possibility that this increase in free water clearance following administration of an ₂-adrenoceptor agonist was associated with a reduction in medullary AQP-2 expression. In the anesthetized rat, clonidine increased urine flow rate (32 ± 5 versus 137 ± 16 µl/min, p < .05) and free water clearance (58 ± 6 versus 3 ± 8 µl/min, p < .05) compared with the group receiving the saline vehicle infusion. The increase in free water clearance with clonidine administration was associated with a reduction in whole kidney AQP-2 mRNA levels (282 ± 25 versus 216 ± 11 A units, p < .05). This decrease in water reabsorption was associated with a redistribution of AQP-2 away from the luminal membrane of the medullary collecting duct to the cytosol. These effects were not secondary to changes in serum vasopressin levels, as these were similar in the vehicle control and clonidine groups (59 ± 5 pg/ml versus 64 ± 7 pg/ml, p = NS). The rapid redistribution of AQP-2 and the reduction in AQP-2 mRNA following clonidine administration are consistent with the hypothesis that the ₂ adrenoceptor regulates water excretion at least in part by effects on AQP-2.