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

• Published in: American journal of physiology. Renal physiology 2008-03, Vol.294 (3), p.F638-F644
• Main Authors: Rieg, Timo, Pothula, Kanishka, Schroth, Jana, Satriano, Joseph, Osswald, Hartmut, Schnermann, Jürgen, Insel, Paul A, Bundey, Richard A, Vallon, Volker
• Format: Article
• Language: English
• Subjects: Animals; Arginine Vasopressin - metabolism; Cyclic AMP - metabolism; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Deamino Arginine Vasopressin - pharmacology; Endothelin-1 - metabolism; In Vitro Techniques; Kidney Tubules, Collecting - metabolism; Male; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase Type III - metabolism; Polymerase Chain Reaction; Receptor, Adenosine A1 - genetics; Receptor, Adenosine A1 - metabolism; Receptors, Prostaglandin E - metabolism; Receptors, Prostaglandin E, EP3 Subtype; Receptors, Purinergic P2 - metabolism; Receptors, Purinergic P2Y2; Receptors, Vasopressin - agonists; Water - metabolism
• ISSN: 1931-857X
• DOI: 10.1152/ajprenal.00344.2007

Activation of adenosine A(1) receptors (A(1)R) 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 A(1)R, we performed experiments in mice lacking A(1)R (A(1)R(-/-)). We assessed the effects of the vasopressin V(2) receptor (V(2)R) 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 ( approximately 2-fold) in A(1)R(-/-) compared with wild-type mice (WT) and, in contrast to WT, was not inhibited by the A(1)R agonist N6-cyclohexyladenosine. A(1)R(-/-) 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 V(2)R antagonist SR121463 or acute water loading; the latter increased inner medullary A(1)R expression in WT. Dose dependence of dDAVP-induced antidiuresis after acute water loading was not different between the genotypes. However, A(1)R(-/-) had greater inner medullary expression of cyclooxygenase-1 under basal conditions and of the P2Y(2) and EP(3) receptor in response to water loading compared with WT mice. Thus vasopressin-induced cAMP formation is enhanced in isolated IMCD of mice lacking A(1)R, but the adenosine-A(1)R/V(2)R interaction demonstrated in vitro is likely compensated in vivo by multiple mechanisms, a number of which can be "uncovered" by water loading.