A novel role for endogenous pituitary adenylate cyclase activating polypeptide in the magnocellular neuroendocrine system.
Central release of vasopressin (VP) by the magnocellular neuroendocrine cells (MNCs) responsible for systemic VP release is believed to be important in modulating the activity of these neurons during dehydration. Central VP release from MNC somata and dendrites is stimulated by both dehydration and pituitary adenylate cyclase activating polypeptide (PACAP). Although PACAP is expressed in MNCs, its potential role in the magnocellular response to dehydration is unexplored. The current study demonstrates that prolonged dehydration increases immunoreactivity for PACAP-27, PACAP-38, and the type I PACAP receptor in the supraoptic nucleus (SON) of the rat. In addition, PACAP stimulates local VP release in the euhydrated rat SON in vitro, and this effect is reduced by the PACAP receptor antagonist PAC(6-27) (100 nm), suggesting the participation of PACAP receptors. Concomitant with its effects on local VP release, PACAP also reduces basal glutamate and aspartate release in the euhydrated rat SON. Furthermore, somatodendritic VP release elicited by acute dehydration is blocked by PAC(6-27), suggesting that endogenous PACAP participates in this response. Consistent with this, RIA revealed that local PACAP-38 release within the SON is significantly elevated during acute dehydration. These results suggest that prolonged activation of hypothalamic MNCs is accompanied by up-regulation of PACAP and the type I PACAP receptor in these cells and that somatodendritic VP release in response to acute dehydration is mediated by activation of PACAP receptors by endogenous PACAP released within the SON. A potential role for PACAP in promoting efficient, but not exhaustive, systemic release of VP from MNCs during physiological challenge is discussed.
Gillard
E R
ER
Department of Cell Biology and Neuroscience, University of California, Riverside, 92521, USA. erachelgillard@yahoo.com
León-Olea
M
M
Mucio-Ramírez
S
S
Coburn
C G
CG
Sánchez-Islas
E
E
de Leon
A
A
Mussenden
H
H
Bauce
L G
LG
Pittman
Q J
QJ
Currás-Collazo
M C
MC
D000222:Adaptation, Physiological; D000818:Animals; D003681:Dehydration / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009490:Neurosecretory Systems / Q000166:cytology / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000502:physiology
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D014667:Vasopressins