Format

Send to

Choose Destination
See comment in PubMed Commons below
Neuropharmacology. 2011 May;60(6):842-51. doi: 10.1016/j.neuropharm.2010.12.024. Epub 2010 Dec 25.

Ghrelin-induced activation of cAMP signal transduction and its negative regulation by endocannabinoids in the hippocampus.

Author information

1
Department of Biological Sciences, The University of Texas at Brownsville, 80 Fort Brown, Brownsville, TX 78520, USA.

Abstract

Increasing evidence indicates that the gut peptide ghrelin facilitates learning behavior and memory tasks. The present study demonstrates a cellular signaling mechanism of ghrelin in the hippocampus. Ghrelin stimulated CREB (cAMP response-element binding protein) through the activation of cAMP, protein kinase A (PKA), and PKA-dependent phosphorylation of NR1 subunit of the NMDA receptor. Ghrelin increased phalloidin-binding to F-actin suggesting CREB-induced gene expression might include reorganization of cytoskeletal proteins. The effect was blocked by the antagonist of the ghrelin receptor in spite of the receptor's primary coupling to Gq proteins. We also discovered inhibitory effect of endocannabinoids on ghrelin-induced NR1 phosphorylation and CREB activity. 2-arachidonoylglycerol (2-AG) exerted its inhibitory effect in the Type 1 cannabinoid receptor (CB1R)-dependent manner, while anandamide's inhibitory effect persisted in the presence of antagonists of CB1R and the vanilloid receptor, suggesting that anandamide might directly inhibit NMDA receptor/channels. Our findings may explain how ghrelin and endocannabinoids regulate hippocampal appetitive learning and plasticity.

PMID:
21187104
PMCID:
PMC3051029
DOI:
10.1016/j.neuropharm.2010.12.024
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Grant support

Publication type

MeSH terms

Substances

Grant support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center