title: Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in melatonin release via the specific receptor PACAP-r1, but not in the circadian oscillator, in chick pineal cells.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates melatonin release from pineal cells and modulates glutamatergic regulation of the suprachiasmatic circadian clock in rodents. We investigated whether PACAP is involved in melatonin release and the circadian oscillation system in chick pineal cells, and if so, whether its effects are mediated by the PACAP-specific receptor (PACAP-r1) or the vasoactive intestinal polypeptide (VIP) receptor. Chick pineal cells were maintained for 4 days under a 12-h light/dark cycle, and thereafter in constant darkness. In the dose-range 10(-10) to 10(-6) M, PACAP increased melatonin release dose-dependently during the 12-h light period on day 3 of culture, and the degree of stimulation was greater than that produced by VIP. VIP receptor antagonists only slightly inhibited PACAP-stimulated melatonin release. Simultaneous addition of VIP and PACAP produced almost additive melatonin release. Under constant dark conditions, 6-h pulses of PACAP started at zeitgeber times (ZT) 15, 21, 3 and 9 h in separate groups of pineal cells did not cause any phase shift in their melatonin rhythm. In addition, PACAP did not affect the light-induced phase advance (ZT 15 h) and delay (ZT 9 h) in melatonin rhythms. The expression of mRNA for the PACAP-r1 (including its splicing variant with a hop cassette) was observed in chick pineal cells. These results suggest that PACAP participates in melatonin release, but not in the circadian oscillator system, via the specific receptor PACAP-r1 in chick pineal cells.
authors.affiliation: Department of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2155, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakahara
authors.forename: Yuri
authors.initials: Y
authors.lastname: Abe
authors.forename: Takayuki
authors.initials: T
authors.lastname: Murakami
authors.forename: Kunio
authors.initials: K
authors.lastname: Shiota
authors.forename: Noboru
authors.initials: N
authors.lastname: Murakami
mesh_terms: D000818:Animals; D002645:Chickens; D002940:Circadian Rhythm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008550:Melatonin / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D008550:Melatonin