Impaired somatodendritic responses to pituitary adenylate cyclase-activating polypeptide (PACAP) of supraoptic neurones in PACAP type I -receptor deficient mice.
The role of pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptor (PAC1 receptor) in regulating hypothalamic supraoptic neurones was investigated using PAC1 receptor-deficient male mice (PAC1-/-). The effects of PACAP on [Ca2+]i were investigated in freshly dissociated supraoptic neurones and on the somatodendritic release of vasopressin and oxytocin, examined on intact supraoptic nuclei. In supraoptic neurones from wild-type mice (PAC1+/+), 100 nm PACAP induced an increase in [Ca2+]i and release of vasopressin and oxytocin, whereas in heterozygous (PAC1+/-) and null-mutant mice (PAC1-/-), PACAP was much less effective. PACAP had no effect on these two parameters when applied to isolated neurohypophysial nerve terminals of PAC1+/+ and PAC1-/- mice, and rats. In conclusion, the PAC1 receptor is solely responsible for the PACAP-induced [Ca2+]i signalling and secretion of vasopressin and oxytocin in the somatodendritic region of supraoptic neurones.
Jamen
F
F
UPR 9023-CNRS and UMR 5101-CNRS, CCIPE, Montpellier, France.
Alonso
G
G
Shibuya
I
I
Widmer
H
H
Vacher
C-M
CM
Calas
A
A
Bockaert
J
J
Brabet
P
P
Dayanithi
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D003712:Dendrites / Q000187:drug effects*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009411:Nerve Endings / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D009994:Osmolar Concentration; D010121:Oxytocin / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010904:Pituitary Gland, Posterior / Q000378:metabolism / Q000648:ultrastructure; D020033:Protein Isoforms / Q000172:deficiency; D051381:Rats; D017208:Rats, Wistar; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000172:deficiency*; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism
C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; C495504:Adcyap1r1 protein, mouse; C495505:Adcyap1r1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D020033:Protein Isoforms; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D014667:Vasopressins; D010121:Oxytocin; D002118:Calcium