title: Characterization of the thermoregulatory response to pituitary adenylate cyclase-activating polypeptide in rodents.
abstract: Administration of the long form (38 amino acids) of pituitary adenylate cyclase-activating polypeptide (PACAP38) into the central nervous system causes hyperthermia, suggesting that PACAP38 plays a role in the regulation of deep body temperature (T b). In this study, we investigated the thermoregulatory role of PACAP38 in details. First, we infused PACAP38 intracerebroventricularly to rats and measured their T b and autonomic thermoeffector responses. We found that central PACAP38 infusion caused dose-dependent hyperthermia, which was brought about by increased thermogenesis and tail skin vasoconstriction. Compared to intracerebroventricular administration, systemic (intravenous) infusion of the same dose of PACAP38 caused significantly smaller hyperthermia, indicating a central site of action. We then investigated the thermoregulatory phenotype of mice lacking the Pacap gene (Pacap (-/-)). Freely moving Pacap (-/-) mice had higher locomotor activity throughout the day and elevated deep T b during the light phase. When the Pacap (-/-) mice were loosely restrained, their metabolic rate and T b were lower compared to their wild-type littermates. We conclude that PACAP38 causes hyperthermia via activation of the autonomic cold-defense thermoeffectors through central targets. Pacap (-/-) mice express hyperkinesis, which is presumably a compensatory mechanism, because under restrained conditions, these mice are hypometabolic and hypothermic compared to controls.
authors.affiliation: Department of Anatomy PTE-MTA "Lendulet" PACAP Research Team, Medical School, University of Pecs, Pecs, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Banki
authors.forename: Eszter
authors.initials: E
authors.lastname: Pakai
authors.forename: Balazs
authors.initials: B
authors.lastname: Gaszner
authors.forename: Csaba
authors.initials: C
authors.lastname: Zsiboras
authors.forename: Andras
authors.initials: A
authors.lastname: Czett
authors.forename: Paras Rahul Parkash
authors.initials: PR
authors.lastname: Bhuddi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Gabor
authors.initials: G
authors.lastname: Toth
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamas
authors.forename: Dora
authors.initials: D
authors.lastname: Reglodi
authors.forename: Andras
authors.initials: A
authors.lastname: Garami
mesh_terms: D000818:Animals; D005260:Female; D005334:Fever / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D022722:Thermogenesis / Q000187:drug effects*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide