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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0134v1 202/3/453    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Roberts, E. Articles by O'Carroll, A.-M. PubMed PubMed Citation Articles by Roberts, E. Articles by O'Carroll, A.-M.

E Roberts, Henry Wellcome LINE, University of Bristol, Bristol, United Kingdom
M Newson, Henry Wellcome LINE, University of Bristol, Bristol, United Kingdom
G Pope, Henry Wellcome LINE, University of Bristol, Bristol, United Kingdom
R Landgraf, Max Planck Institute of Psychiatry, Munich, Germany
S Lolait, Henry Wellcome LINE, University of Bristol, Bristol, United Kingdom
A O'Carroll, Henry Wellcome LINE, University of Bristol, Bristol, BS1 3NY, United Kingdom

Correspondence: Anne-Marie O'Carroll, Email: A.M.OCarroll{at}bristol.ac.uk

The apelinergic system, comprised of apelin and its G protein-coupled receptor APJ, is expressed within key regions of the central nervous system associated with vasopressin synthesis and release as well as in structures involved in the control of drinking behavior, including the magnocellular neurones of the hypothalamus, circumventricular organs and the pituitary gland. This localisation is indicative of a possible functional role in fluid homeostasis. We investigated a role for APJ in the regulation of fluid balance using mice deficient for the receptor. Male APJ wildtype and knockout (APJ-/-) mice were housed in metabolic cages to allow determination of water intake and urine volume and osmolality. When provided with free access to water APJ-/- mice drank significantly less than wildtypes, while their urine volume and osmolality did not differ. Water deprivation for 24 hours significantly reduced urine volume and increased osmolality in wildtype but not in APJ-/- mice. Baseline plasma vasopressin concentration increased comparably in both wildtype and APJ-/- following dehydration, however APJ-/- mice were unable to concentrate their urine to the same extent as wildtype mice in response to the V2 agonist desmopressin. Analysis of c-fos mRNA expression in response to dehydration showed attenuation of expression within the subfornical organ, accentuated expression in the paraventricular nucleus, but no differences in expression in the supraoptic nucleus nor median preoptic nucleus in APJ-/- mice compared to wildtype. These findings demonstrate a physiological role for APJ in mechanisms of water intake and fluid retention and suggest an antidiuretic effect of apelin in vivo.

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