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Pituitary adenylate cyclase-activating polypeptide 6-38 blocks cocaine- and amphetamine-regulated transcript Peptide-induced hypophagia in rats.

Abstract
Cocaine- and amphetamine-regulated transcript peptides (CARTp) suppress nutritional intake after administration into the fourth intracerebral ventricle. Recent in vitro studies have shown that PACAP 6-38, a pituitary adenylate cyclase-activating polypeptide (PACAP) fragment, could act as a competitive antagonist against CARTp 55-102 on a common CARTp-sensitive receptor structure. Here, we show for the first time in vivo that the reduction in solid food intake induced by exogenous CARTp 55-102 (0.3 nmol: 1.5 µg) administered fourth i.c.v. is blocked by pretreatment with PACAP 6-38 (3 nmol). The PACAP 6-38 fragment had no effect by itself either when given into the fourth ventricle or subcutaneously. Although effective to block the CARTp-effect on feeding and short-term body weight, PACAP 6-38 failed to attenuate CARTp-associated gross motor behavioral changes suggesting at least two CARTp-sensitive receptor subtypes. In conclusion, PACAP 6-38 acts as a functional CARTp antagonist in vivo and blocks its effects on feeding and short term weight gain.
AuthorsJonathan R Burgos, Britt-Marie Iresjö, Ulrika Smedh
JournalPloS one (PLoS One) Vol. 8 Issue 8 Pg. e72347 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23967296 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • cocaine- and amphetamine-regulated transcript protein
  • pituitary adenylate-cyclase-activating-peptide (6-38)
Topics
  • Analysis of Variance
  • Animals
  • Feeding Behavior (drug effects)
  • Feeding and Eating Disorders (drug therapy, etiology)
  • Male
  • Nerve Tissue Proteins (antagonists & inhibitors)
  • Peptide Fragments (administration & dosage, pharmacology)
  • Pituitary Adenylate Cyclase-Activating Polypeptide (administration & dosage, pharmacology)
  • Rats

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