Faculty Collaboration Database

Inhibition of food intake by PACAP in the hypothalamic ventromedial nuclei is mediated by NMDA receptors. Physiol Behav 2014 Jun 22;133:230-5

Date

06/01/2014

Pubmed ID

24878316

Pubmed Central ID

PMC4126770

DOI

10.1016/j.physbeh.2014.05.029

Scopus ID

2-s2.0-84902497963 (requires institutional sign-in at Scopus site)   31 Citations

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.

Author List

Resch JM, Maunze B, Phillips KA, Choi S

Author

Sujean Choi PhD in the School of Allied Health department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Arabidopsis Proteins
Eating
Excitatory Amino Acid Antagonists
Feeding Behavior
Male
Neurotransmitter Agents
Nuclear Proteins
Phosphorylation
Pituitary Adenylate Cyclase-Activating Polypeptide
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate
Time Factors
Tyrosine
Valine
Ventromedial Hypothalamic Nucleus