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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/F638    most recent 00344.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rieg, T. Articles by Vallon, V. Search for Related Content PubMed PubMed Citation Articles by Rieg, T. Articles by Vallon, V.

Vasopressin regulation of inner medullary collecting ducts and compensatory changes in mice lacking adenosine A₁ receptors

Departments of ¹Medicine and ²Pharmacology, University of California, ³Veterans Affairs San Diego Healthcare System, San Diego, California; ⁴National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; and ⁵Institute of Pharmacology and Toxicology, Medical Faculty of Eberhard Karls University, Tübingen, Germany

Submitted 23 July 2007 ; accepted in final form 14 January 2008

Activation of adenosine A₁ receptors (A₁R) can inhibit arginine vasopressin (AVP)-induced cAMP formation in isolated cortical and medullary collecting ducts. To assess the in vivo consequences of the absence of A₁R, we performed experiments in mice lacking A₁R (A₁R^–/–). We assessed the effects of the vasopressin V₂ receptor (V₂R) agonist 1-desamino-8-D-arginine vasopressin (dDAVP) on cAMP formation in isolated inner medullary collecting ducts (IMCD) and on water excretion in conscious water-loaded mice. dDAVP-induced cAMP formation in isolated IMCD was significantly greater (2-fold) in A₁R^–/– compared with wild-type mice (WT) and, in contrast to WT, was not inhibited by the A₁R agonist N6-cyclohexyladenosine. A₁R^–/– and WT had similar basal urinary excretion of vasopressin, expression of aquaporin-2 protein in renal cortex and medulla, and acute increases in urinary flow rate and electrolyte-free water clearance in response to the V₂R antagonist SR121463 or acute water loading; the latter increased inner medullary A₁R expression in WT. Dose dependence of dDAVP-induced antidiuresis after acute water loading was not different between the genotypes. However, A₁R^–/– had greater inner medullary expression of cyclooxygenase-1 under basal conditions and of the P2Y₂ and EP₃ receptor in response to water loading compared with WT mice. Thus vasopressin-induced cAMP formation is enhanced in isolated IMCD of mice lacking A₁R, but the adenosine-A₁R/V₂R interaction demonstrated in vitro is likely compensated in vivo by multiple mechanisms, a number of which can be "uncovered" by water loading.

arginine vasopressin; aquaporin-2; cyclooxygenase