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The functional cooperation of 5-HT1A and mGlu4R in HEK-293 cell line.

Authors
  • Burnat, Grzegorz1
  • Brański, Piotr2
  • Solich, Joanna3
  • Kolasa, Magdalena3
  • Chruścicka, Barbara2
  • Dziedzicka-Wasylewska, Marta3
  • Pilc, Andrzej4, 5
  • 1 Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, 31-343, Kraków, Poland. [email protected] , (Poland)
  • 2 Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, 31-343, Kraków, Poland. , (Poland)
  • 3 Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, 31-343, Kraków, Poland. , (Poland)
  • 4 Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, 31-343, Kraków, Poland. [email protected] , (Poland)
  • 5 Drug Management Department, Faculty of Health Sciences, Institute of Public Health, Jagiellonian University Collegium Medicum, Grzegorzecka 20, 31-531, Kraków, Poland. [email protected] , (Poland)
Type
Published Article
Journal
Pharmacological Reports
Publisher
Elsevier
Publication Date
Oct 01, 2020
Volume
72
Issue
5
Pages
1358–1369
Identifiers
DOI: 10.1007/s43440-020-00114-1
PMID: 32472388
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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). 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. 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.

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