Academic Journal
Presynaptic 5-HT2A-mGlu2/3 Receptor-Receptor Crosstalk in the Prefrontal Cortex: Metamodulation of Glutamate Exocytosis
| العنوان: | Presynaptic 5-HT2A-mGlu2/3 Receptor-Receptor Crosstalk in the Prefrontal Cortex: Metamodulation of Glutamate Exocytosis |
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| المؤلفون: | Taddeucci, Alice, Olivero, Guendalina, Roggeri, Alessandra, Milanese, Claudio, Giorgio, Francesco Paolo Di, Grilli, Massimo, Marchi, Mario, Garrone, Beatrice, Pittaluga, Anna |
| المساهمون: | Taddeucci, Alice, Olivero, Guendalina, Roggeri, Alessandra, Milanese, Claudio, Giorgio, Francesco Paolo Di, Grilli, Massimo, Marchi, Mario, Garrone, Beatrice, Pittaluga, Anna |
| بيانات النشر: | MDPI ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND |
| سنة النشر: | 2022 |
| المجموعة: | Università degli Studi di Genova: CINECA IRIS |
| مصطلحات موضوعية: | 5-HT2A receptor, clozapine, glutamate exocytosis, mGlu2 3 receptor, prefrontal cortex, synaptosome, trazodone, Animals, Autoreceptors, D Aspartic Acid, Exocytosis, Glutamic Acid, Ketanserin, Rats, Receptor, Serotonin, 5 HT2A, Receptors, Metabotropic Glutamate |
| الوصف: | The glutamatergic nerve endings of a rat prefrontal cortex (PFc) possess presynaptic 5-HT2A heteroreceptors and mGlu2/3 autoreceptors, whose activation inhibits glutamate exocytosis, and is measured as 15 mM KCl-evoked [H-3]D-aspartate ([H-3]D-asp) release (which mimics glutamate exocytosis). The concomitant activation of the two receptors nulls their inhibitory activities, whereas blockade of the 5-HT2A heteroreceptors with MDL11,939 (1 mu M) strengthens the inhibitory effect elicited by the mGlu2/3 receptor agonist LY329268 (1 mu M). 5-HT2A receptor antagonists (MDL11,939; ketanserin; trazodone) amplify the impact of low (3 nM) LY379268. Clozapine (0.1-10 mu M) mimics the 5-HT2A agonist (+/-) DOI and inhibits the KCl-evoked [H-3]D-asp overflow in a MDL11,939-dependent fashion, but does not modify the (+/-) DOI-induced effect. mGlu2 and 5-HT2A proteins do not co-immunoprecipitate from synaptosomal lysates, nor does the incubation of PFc synaptosomes with MDL11,939 (1 mu M) or clozapine (10 mu M) modify the insertion of mGlu2 subunits in synaptosomal plasma membranes. In conclusion, 5-HT2A and mGlu2/3 receptors colocalize, but do not physically associate, in PFc glutamatergic terminals, where they functionally interact in an antagonist-like fashion to control glutamate exocytosis. The mGlu2/3-5-HT2A metamodulation could be relevant to therapy for central neuropsychiatric disorders, including schizophrenia, but also unveil cellular events accounting for their development, which also influence the responsiveness to drugs regimens. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/36230998; info:eu-repo/semantics/altIdentifier/wos/WOS:000866705100001; volume:11; firstpage:3035; lastpage:3050; numberofpages:16; journal:CELLS; https://hdl.handle.net/11567/1099319; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85139760110 |
| DOI: | 10.3390/cells11193035 |
| الاتاحة: | https://hdl.handle.net/11567/1099319 https://doi.org/10.3390/cells11193035 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E6F162C6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cells11193035 |
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