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

Am J Physiol Renal Physiol. 2008 Mar;294(3):F638-44. doi: 10.1152/ajprenal.00344.2007. Epub 2008 Jan 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 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*


  • Endothelin-1
  • Membrane Proteins
  • P2ry2 protein, mouse
  • Ptger3 protein, mouse
  • Receptor, Adenosine A1
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP3 Subtype
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y2
  • Receptors, Vasopressin
  • Water
  • Arginine Vasopressin
  • Cyclic AMP
  • Nitric Oxide Synthase Type III
  • Ptgs2 protein, mouse
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Ptgs1 protein, mouse
  • Deamino Arginine Vasopressin