Stimulus-specific neuroendocrine responses to osmotic challenges in apelin receptor knockout mice.
The expression of the novel peptide apelin and its receptor APJ within specific regions of the brain, in particular the magnocellular neurones of the hypothalamus and the circumventricular organs, has implicated the apelinergic system in mechanisms controlling fluid homeostasis. In addition, apelin and APJ are considered to be involved in controlling arginine vasopressin (AVP) secretion into the circulation and release within the hypothalamic-neurohypophysial system. To clarify the role of APJ during regulation of fluid homeostasis, we compared the effects of osmotic stimulation on the urinary concentrating capacities and central nervous system responses of salt-loaded (SL) and water-deprived (WD) female APJ knockout (APJ(-/-)) mice and wild-type controls. SL resulted in a significantly increased urine volume in APJ(-/-) mice compared to wild-type controls, whereas WD in APJ(-/-) mice failed to reduce urine volume as seen in wild-type controls. AVP transcripts in the supraoptic and paraventricular nuclei and plasma AVP concentrations were significantly attenuated in SL APJ(-/-) mice compared to SL wild-type, but increased comparably in wild-type and APJ(-/-) mice after WD. Analysis of c-fos mRNA expression in the median preoptic nucleus and subfornical organ in response to either WD or SL showed attenuated expression in APJ(-/-) compared to wild-type mice. These findings further implicate the apelinergic system in mechanisms controlling fluid homeostasis, particularly at a neuroendocrine level, and suggest stimulus-specific involvement in vasopressinergic activity.
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK.
E M
EM
Roberts
G R
GR
Pope
M J F
MJ
Newson
R
R
Landgraf
S J
SJ
Lolait
A-M
AM
O'Carroll
D000818:Animals; D000075244:Apelin Receptors; D001826:Body Fluids / Q000378:metabolism / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009490:Neurosecretory Systems / Q000378:metabolism / Q000502:physiology*; D009997:Osmotic Pressure / Q000502:physiology; D010812:Physical Stimulation; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000502:physiology; D012492:Salts / Q000494:pharmacology; D013312:Stress, Physiological / Q000502:physiology; D014667:Vasopressins / Q000378:metabolism; D014868:Water Deprivation / Q000502:physiology; D014883:Water-Electrolyte Imbalance / Q000097:blood / Q000503:physiopathology / Q000652:urine
D000075244:Apelin Receptors; C491285:Aplnr protein, mouse; D043562:Receptors, G-Protein-Coupled; D012492:Salts; D014667:Vasopressins