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Research ArticleArticle

Regulation of Aquaporin-2 Expression by the α2-Adrenoceptor Agonist Clonidine in the Rat

Asad Junaid, Li Cui, S. Brian Penner and Donald D. Smyth
Journal of Pharmacology and Experimental Therapeutics November 1999, 291 (2) 920-923;
Asad Junaid
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Li Cui
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S. Brian Penner
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Donald D. Smyth
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Abstract

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. α2-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 α2-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 ± 11A 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 α2 adrenoceptor regulates water excretion at least in part by effects on AQP-2.

Footnotes

  • Send reprint requests to: Dr. Asad Junaid, Department of Internal Medicine, Faculty of Medicine, BG007 St. Boniface Hospital, Winnipeg R2H 2A6, Manitoba. E-mail:junaid{at}cc.umanitoba.ca

  • ↵1 Supported by funding from the Medical Research Council of Canada (to D.D.S.) and Health Sciences Center Foundation of Winnipeg (to A.J.).

  • Abbreviations:
    aquaporin-2
    AQP-2
    • Received February 19, 1999.
    • Accepted July 25, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 2
1 Nov 1999
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Research ArticleArticle

Regulation of Aquaporin-2 Expression by the α2-Adrenoceptor Agonist Clonidine in the Rat

Asad Junaid, Li Cui, S. Brian Penner and Donald D. Smyth
Journal of Pharmacology and Experimental Therapeutics November 1, 1999, 291 (2) 920-923;

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Research ArticleArticle

Regulation of Aquaporin-2 Expression by the α2-Adrenoceptor Agonist Clonidine in the Rat

Asad Junaid, Li Cui, S. Brian Penner and Donald D. Smyth
Journal of Pharmacology and Experimental Therapeutics November 1, 1999, 291 (2) 920-923;
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