Pharmacological stimulation of galanin receptor 1 but not galanin receptor 2 attenuates kainic acid-induced neuronal cell death in the rat hippocampus
(English)Manuscript (preprint) (Other academic)
The neuropeptide galanin is widely distributed in the central and peripheral nervous systems. Galanin is part of a bigger family of bioactive peptides and its biological activity is mediated through three G-protein coupled receptor subtypes, GalR1-3. The last 20 years have provided data supporting a neuroprotective effect of galanin that probably is mediated through the activation of GalR1 and GalR2.
In this study, an additional galanin receptor ligand, M1154, was developed to fully address the pharmaceutical potential of galanin receptor subtype selective ligands to inhibit excitotoxic cell death. We thereafter adapted a single protocol for signaling assay for all three galanin receptors, by utilizing a non-labeled real time instrument, to ease classification of novel ligands according to their ability to activate the different galanin receptor subtypes. M1154 is a GalR1/2 selective ligand in our binding and signaling assays with no detectable interaction with GalR3.
The novel M1154 peptide was compared to earlier published selective ligands, namely M617 and M1145, in its ability to reduce the excitotoxic effects of kainic acid (KA). While no significant difference in the time course or severity of induced seizure activity was observed, administration of either M617 or M1154 before KA administration, significantly attenuated the neuronal cell death in the hippocampus. Our results clearly show the potential therapeutic value of agonists selective for GalR1 as neuroprotective agents for the prevention of excitotoxic neuronal cell death.
GPCR, galanin, neuropeptide, galanin receptor, GalR1, label free real time technology, excitotoxicity, M1154
Neurosciences Biochemistry and Molecular Biology
Research subject Neurochemistry with Molecular Neurobiology
IdentifiersURN: urn:nbn:se:su:diva-75087OAI: oai:DiVA.org:su-75087DiVA: diva2:514066