Signal Transduction Pathway Gene Regulation by Long‐Term Treatment with CART Peptide

Abstract

The cocaine‐ and amphetamine‐regulated transcript (CART) was first isolated from rat striatum following the acute administration of cocaine or amphetamine. It was quickly determined that CART or CART peptide was expressed in a variety of tissues affecting a wide range of important processes. Although the identity of the CART receptor has not been discovered, its ability to stimulate ERK1/2 in a pertussis‐sensitive manner, and to inhibit AKT phosphorylation suggests that it is a G‐protein coupled receptor (GPCR) coupled to an inhibitory G protein. To gain further insight into the identity of the CART peptide receptor, we investigated the effects of CART peptide activation on other pathways by subjecting differentiated PC12 cells to long‐term (24 hour) incubation with CART peptide. Changes in mRNA expression were assessed using PCR arrays with cDNA probes for a variety of general signal transduction proteins or proteins involved in Gi signaling. Changes in genes related to cAMP and AKT signaling pathways as well as changes in genes for proteins involved in the ERK1/2 activation pathway were observed. Specifically, upregulation of Atf4, SLC2a1 and Map2k2 were noted. Further study of these pathways may provide additional information that will lead to the identification of the CART peptide receptor and therapeutic uses for the CART peptide.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.