The functional cooperation of 5-HT 1A and mGlu4R in HEK-293 cell line
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ARTICLE
The functional cooperation of 5‑HT1A and mGlu4R in HEK‑293 cell line Grzegorz Burnat1 · Piotr Brański1 · Joanna Solich2 · Magdalena Kolasa2 · Barbara Chruścicka1 · Marta Dziedzicka‑Wasylewska2 · Andrzej Pilc1,3 Received: 18 March 2020 / Revised: 21 May 2020 / Accepted: 25 May 2020 © The Author(s) 2020
Abstract Background The serotonin 5-HT1A receptor (5-HT1AR) and metabotropic glutamate receptor 4 (mGlu4) have been implicated as sites of antipsychotic drug action. 5-HT1AR belongs to the A class of G protein-coupled receptors (GPCRs); mGlu4 is a representative of class C GPCRs. Both receptors preferentially couple with Gi protein to inhibit cAMP formation. The present work aimed to examine the possibility of mGlu4 and 5-HT1A receptor cross-talk, the phenomenon that could serve as a molecular basis of the interaction of these receptor ligands observed in behavioral studies. Methods First, in vitro studies were performed to examine the pharmacological modulation of interaction of the mGlu4 and 5-HT1A receptors in the T-REx 293 cell line using SNAP- or HALO–tag and cAMP accumulation assay. Next, the colocalization of these two receptors was examined in some regions of the mouse brain by applying RNAScope dual fluorescence in situ hybridization, immunohistochemical labeling, and proximity ligation assay (PLA). Results The ex vivo and in vitro results obtained in the present work suggest the existence of interactions between mGlu4 and 5-HT1A receptors. The changes were observed in cAMP accumulation assay and were dependent on expression and activation of mGlu4R in T-REx 293cell line. Moreover, the existence of spots with proximity expression of both receptors were showed by PLA, immunofluorescence labeling and RNAscope methods. Conclusion The existence of interactions between mGlu4 and 5-HT1A receptors may represent another signaling pathway involved in the development and treatment psychiatric disorders such as schizophrenia or depression. Keywords Cell signaling · Gpcrs · Cross-talk · mGlu4 receptors · 5-HT1A receptors
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43440-020-00114-1) contains supplementary material, which is available to authorized users. * Grzegorz Burnat burnat@if‑pan.krakow.pl * Andrzej Pilc nfpilc@cyf‑kr.edu.pl 1
Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, 31‑343 Kraków, Poland
2
Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, 31‑343 Kraków, Poland
3
Drug Management Department, Faculty of Health Sciences, Institute of Public Health, Jagiellonian University Collegium Medicum, Grzegorzecka 20, 31‑531 Kraków, Poland
The G protein-coupled receptors (GPCRs) form the largest and most diverse receptor superfamily in mammals [1]. The International Human Genome Sequencing Consortium reported a total of 569 rhodopsin-like GPCRs [2]. It has been estimated that approximately 34–50% of all modern d
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