Differential signaling signatures evoked by DOI versus lisuride stimulation of the 5-HT 2A receptor.

Authors :: Banerjee AA
Vaidya VA
Source :: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Oct 22; Vol. 531 (4), pp. 609-614. Date of Electronic Publication: 2020 Aug 16.
Publication Year :: 2020
Abstract: The 5-HT <subscript>2A</subscript> receptor is a target for hallucinogenic and non-hallucinogenic ligands that evoke unique behavioral, electrophysiological and molecular consequences. Here, we explored the differential effects of distinct 5-HT <subscript>2A</subscript> receptor ligands on signaling pathways downstream to the 5-HT <subscript>2A</subscript> receptor. The hallucinogenic 5-HT <subscript>2A</subscript> receptor agonist DOI evoked an enhanced signaling response compared to the non-hallucinogenic 5-HT <subscript>2A</subscript> receptor agonist lisuride in human/rat 5-HT <subscript>2A</subscript> R-EGFP receptor expressing HEK293 cell lines and cortical neuronal cultures. We noted higher levels of phospho-PLC, pPKC, pERK, pCaMKII, pCREB, as well as higher levels of IP3 and DAG production following 5-HT <subscript>2A</subscript> receptor stimulation with DOI. Our study reveals distinct signaling signatures, differing in magnitude and kinetics at the 5-HT <subscript>2A</subscript> receptor in response to DOI versus lisuride.<br />Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)

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