Inhibition of food intake by PACAP in the hypothalamic ventromedial nuclei is mediated by NMDA receptors

Jon M Resch; Brian Maunze; Kailynn A Phillips; SuJean Choi

doi:10.1016/j.physbeh.2014.05.029

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Inhibition of food intake by PACAP in the hypothalamic ventromedial nuclei is mediated by NMDA receptors

Journal article

Open access

Peer reviewed

Inhibition of food intake by PACAP in the hypothalamic ventromedial nuclei is mediated by NMDA receptors

Jon M Resch, Brian Maunze, Kailynn A Phillips and SuJean Choi

Physiology & behavior, Vol.133, pp.230-235

06/22/2014

DOI: 10.1016/j.physbeh.2014.05.029

PMCID: PMC4126770

PMID: 24878316

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Abstract

Central injections of pituitary adenylate cyclase-activating polypeptide (PACAP) into the ventromedial nuclei (VMN) of the hypothalamus produce hypophagia that is dependent upon the PAC1 receptor; however, the signaling downstream of this receptor in the VMN is unknown. Though PACAP signaling has many targets, this neuropeptide has been shown to influence glutamate signaling in several brain regions through mechanisms involving NMDA receptor potentiation via activation of the Src family of protein tyrosine kinases. With this in mind, we examined the Src-NMDA receptor signaling pathway as a target for PACAP signaling in the VMN that may mediate its effects on feeding behavior. Under nocturnal feeding conditions, NMDA receptor antagonism prior to PACAP administration into the VMN attenuated PACAP-mediated decreases in feeding suggesting that glutamatergic signaling via NMDA receptors is necessary for PACAP-induced hypophagia. Furthermore, PACAP administration into the VMN resulted in increased tyrosine phosphorylation of the GluN2B subunit of the NMDA receptor, and inhibition of Src kinase activity also blocked the effects of PACAP administration into the VMN on feeding behavior. These results indicate that PACAP neurotransmission in the VMN likely augments glutamate signaling by potentiating NMDA receptors activity through the tyrosine phosphorylation events mediated by the Src kinase family, and modulation of NMDA receptor activity by PACAP in the hypothalamus may be a primary mechanism for its regulation of food intake.

Ventromedial Hypothalamic Nucleus - drug effects

Valine - analogs & derivatives

Receptors, N-Methyl-D-Aspartate - metabolism

Rats

Male

Ventromedial Hypothalamic Nucleus - metabolism

Excitatory Amino Acid Antagonists - pharmacology

Rats, Sprague-Dawley

Feeding Behavior - drug effects

Nuclear Proteins

Eating - drug effects

Tyrosine - metabolism

Animals

Arabidopsis Proteins

Time Factors

Neurotransmitter Agents - pharmacology

Pituitary Adenylate Cyclase-Activating Polypeptide - pharmacology

Phosphorylation - drug effects

Valine - pharmacology

Details

Title: Subtitle: Inhibition of food intake by PACAP in the hypothalamic ventromedial nuclei is mediated by NMDA receptors
Creators: Jon M Resch - Department of Biomedical Sciences, Marquette University, Milwaukee, WI 53201, USA
Brian Maunze - Department of Biomedical Sciences, Marquette University, Milwaukee, WI 53201, USA
Kailynn A Phillips - Department of Biomedical Sciences, Marquette University, Milwaukee, WI 53201, USA
SuJean Choi - Department of Biomedical Sciences, Marquette University, Milwaukee, WI 53201, USA. Electronic address: sujean.choi@marquette.edu
Resource Type: Journal article
Publication Details: Physiology & behavior, Vol.133, pp.230-235
DOI: 10.1016/j.physbeh.2014.05.029
PMID: 24878316
PMCID: PMC4126770
NLM abbreviation: Physiol Behav
ISSN: 0031-9384
eISSN: 1873-507X
Publisher: United States
Grant note: DK074734 / NIDDK NIH HHS R01 DK074734 / NIDDK NIH HHS
Language: English
Date published: 06/22/2014
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984065854802771

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