Neuropeptide Y2 receptors on nerve endings from the rat neurohypophysis regulate vasopressin and oxytocin release.
Neuropeptide Y and peptide YY are important central and peripheral modulators of cardiovascular and neuroendocrine functions, that act through multiple receptor subtypes, Y1 through Y5. A neuropeptide Y-binding site of the Y2 type was characterized by ligand-binding studies in isolated nerve terminals from the rat neurohypophysis. Functionally, neuropeptide Y and peptide YY dose-dependently triggered arginine 8-vasopressin and oxytocin release from perfused isolated terminals, and potentiated the arginine-8-vasopressin release induced by depolarization. Osmotic stimulation by salt loading of rats for two and seven days caused a more than three-fold increase in the neuropeptide Y content of the nerve endings. However, the Y2 receptor expression and arginine-8-vasopressin content declined, showing that the neuropeptide Y system is dynamic and suggesting that it plays a physiological role in salt and water homeostasis. Two sets of observations suggest the arginine-8-vasopressin release by neuropeptide Y may not be explained by neuropeptide Y effects on intracellular Ca2+. First, absence of Ca2+ from the perfusion medium did not affect the arginine-8-vasopressin release, and secondly neuropeptide Y did not change intraterminal Ca2+ concentrations. Pretreatment with pertussis toxin blocked arginine-8-vasopressin secretion by neuropeptide Y, suggesting activation of Gi or Go heterotrimeric G-proteins are required for secretion. It is concluded, that the nerve endings of the neurohypophysis contain a complete neuropeptide Y system with ligand and receptors. Neuropeptide Y may act in an autocrine fashion via activation of Y2 neuropeptide Y receptors to stimulate the release of vasopressin and oxytocin via a Gi/Go dependent secretory mechanism.
Sheikh
S P
SP
Department of Internal Medicine B, University Hospital, Rigshospitalet, Copenhagen, Denmark.
Feldthus
N
N
Orkild
H
H
Göke
R
R
McGregor
G P
GP
Turner
D
D
Møller
M
M
Stuenkel
E L
EL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D009411:Nerve Endings / Q000378:metabolism* / Q000648:ultrastructure; D009994:Osmolar Concentration; D010121:Oxytocin / Q000378:metabolism*; D019894:Peptide YY / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism*
D017476:Receptors, Neuropeptide Y; D019894:Peptide YY; D014667:Vasopressins; D010121:Oxytocin; D002118:Calcium