Salmon calcitonin distributes into the arcuate nucleus to a subset of NPY neurons in mice.
Animals
Arcuate Nucleus of Hypothalamus
/ drug effects
Calcitonin
/ administration & dosage
Calcium-Regulating Hormones and Agents
/ administration & dosage
Cell Line
Cricetinae
Female
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurons
/ drug effects
Neuropeptide Y
/ metabolism
Protein Binding
/ physiology
Rats
Agonist
Amylin
Area postrema
NPY
Whole-brain 3D imaging
Journal
Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217
Informations de publication
Date de publication:
01 05 2020
01 05 2020
Historique:
received:
08
07
2019
revised:
28
01
2020
accepted:
02
02
2020
pubmed:
9
2
2020
medline:
24
4
2021
entrez:
9
2
2020
Statut:
ppublish
Résumé
The amylin receptor (AMY) and calcitonin receptor (CTR) agonists induce acute suppression of food intake in rodents by binding to receptors in the area postrema (AP) and potentially by targeting arcuate (ARC) neurons directly. Salmon calcitonin (sCT) induces more potent, longer lasting anorectic effects compared to amylin. We thus aimed to investigate whether AMY/CTR agonists target key neuronal populations in the ARC, and whether differing brain distribution patterns could mediate the observed differences in efficacy with sCT and amylin treatment. Brains were examined by whole brain 3D imaging and confocal microscopy following subcutaneous administration of fluorescently labelled peptides to mice. We found that sCT, but not amylin, internalizes into a subset of ARC NPY neurons, along with an unknown subset of ARC, AP and dorsal vagal motor nucleus cells. ARC POMC neurons were not targeted. Furthermore, amylin and sCT displayed similar distribution patterns binding to receptors in the AP, the organum vasculosum of the lamina terminalis (OVLT) and the ARC. Amylin distributed within the median eminence with only specs of sCT being present in this region, however amylin was only detectable 10 minutes after injection while sCT displayed a residence time of up to 2 hours post injection. We conclude that AMY/CTR agonists bind to receptors in a subset of ARC NPY neurons and in circumventricular organs. Furthermore, the more sustained and greater anorectic efficacy of sCT compared to rat amylin is not attributable to differences in brain distribution patterns but may more likely be explained by greater potency at both the CTR and AMY.
Identifiants
pubmed: 32035146
pii: S0028-3908(20)30053-8
doi: 10.1016/j.neuropharm.2020.107987
pii:
doi:
Substances chimiques
Calcium-Regulating Hormones and Agents
0
Neuropeptide Y
0
salmon calcitonin
7SFC6U2VI5
Calcitonin
9007-12-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107987Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest KR, LMJ, SL, TG and AS are full-time employees of Novo Nordisk and hold minor share portions as part of their employment. HLZ, JL, TL and CLF declare no competing financial interests.