PACAP deficient mice display reduced carbohydrate intake and PACAP activates NPY-containing neurons in the rat hypothalamic arcuate nucleus.
Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiates both insulin release from islets and insulin action in adipocytes. Therefore, this peptide is considered a regulator of glucose homeostasis. PACAP and its receptors are localized not only in the peripheral tissues but in the central nervous system. The present study examined whether PACAP regulates the feeding behavior and the activity of neurons in the hypothalamic arcuate nucleus (ARC), a feeding center. Food intake was measured in the PACAP knock-out mice. Cytosolic Ca2+ concentration ([Ca2+]i) in single neurons isolated from the ARC of rats was measured by fura-2 microfluorometry, followed by immunocytochemical staining with anti-NPY antiserum. PACAP knock-out mice showed a decrease in the intake of high carbohydrate, but not high fat, food. PACAP increased [Ca2+]i in NPY neurons of the ARC that are implicated in the feeding, particularly the carbohydrate ingestion. Agonists of PACAP receptors, PAC1-R and VPAC2-R, also increased [Ca2+]i. The present study, by demonstrating that PACAP directly reacts with the ARC NPY neurons to increase [Ca2+]i and that ingestion of the carbohydrate-rich food is reduced in PACAP-deficiency, suggests a facilitative role for PACAP in the carbohydrate intake.
Department of Physiology, Division of Integrative Physiology, Jichi Medical School, School of Medicine, Minamikawachi, Tochigi 329-0498, Japan.
Masanori
M
Nakata
Daisuke
D
Kohno
Norihito
N
Shintani
Yuriko
Y
Nemoto
Hitoshi
H
Hashimoto
Akemichi
A
Baba
Toshihiko
T
Yada
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology*; D001522:Behavior, Animal; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D050260:Carbohydrate Metabolism; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000235:genetics; D004435:Eating / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D018377:Neurotransmitter Agents / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000819:agonists; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D018005:Receptors, Vasoactive Intestinal Peptide / Q000819:agonists; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000494:pharmacology
C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; C495504:Adcyap1r1 protein, mouse; C495505:Adcyap1r1 protein, rat; D001786:Blood Glucose; D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010456:Peptides, Cyclic; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; C089777:Ro 25-1553; C495510:Vipr2 protein, mouse; C495511:Vipr2 protein, rat; D014660:Vasoactive Intestinal Peptide; D002118:Calcium