title: Central effects of calcitonin receptor-stimulating peptide-1 on energy homeostasis in rats.
abstract: The CT-R [calcitonin (CT) receptor] is expressed in the central nervous system and is involved in the regulation of food intake, thermogenesis, and behaviors. CT-R-stimulating peptide-1 (CRSP-1), a potent ligand for the CT-R, was recently isolated from the porcine brain. In this study, we first confirmed that porcine CRSP-1 (pCRSP-1) enhanced the cAMP production in COS-7 cells expressing recombinant rat CT-R, and then we examined the central effects of pCRSP-1 on feeding and energy homeostasis in rats. Intracerebroventricular (icv) administration of pCRSP-1 to free-feeding rats suppressed food intake in a dose-dependent manner. Chronic icv infusion of pCRSP-1 suppressed body weight gain over the infusion period. Furthermore, icv administration of pCRSP-1 increased body temperature and decreased locomotor activity. The central effects of pCRSP-1 were more potent than those of porcine CT in rats. In contrast, ip administration of pCRSP-1 did not elicit any anorectic or catabolic effects. Administration icv of pCRSP-1 also induced mild dyskinesia of the lower extremities and decreased gastric acid output. Fos expression induced by icv administration of pCRSP-1 was detected in the neurons of the paraventricular nucleus, dorsomedial hypothalamic nucleus, arcuate nucleus, locus coeruleus, and nucleus of solitary tract, areas that are known to regulate feeding and energy homeostasis. Administration icv of pCRSP-1 increased plasma concentrations of ACTH and corticosterone, implying that the hypothalamic-pituitary-adrenocortical axis might be involved in catabolic effects of pCRSP-1. These results suggest that CRSP-1 can function as a ligand for the CT-R and may act as a catabolic signaling molecule in the central nervous system.
authors.affiliation: Department of Pediatrics, Miyazaki Medical College, University of Miyazaki, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Sawada
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Shimbara
authors.forename: Koji
authors.initials: K
authors.lastname: Toshinai
authors.forename: Muhtashan S
authors.initials: MS
authors.lastname: Mondal
authors.forename: Yukari
authors.initials: Y
authors.lastname: Date
authors.forename: Noboru
authors.initials: N
authors.lastname: Murakami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Katafuchi
authors.forename: Naoto
authors.initials: N
authors.lastname: Minamino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nunoi
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018003:Receptors, Calcitonin / Q000819:agonists*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D008024:Ligands; D018003:Receptors, Calcitonin; D000324:Adrenocorticotropic Hormone; D015740:Calcitonin Gene-Related Peptide; D003345:Corticosterone