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Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains

Somatostatin is an important mood and pain-regulating neuropeptide, which exerts analgesic, anti-inflammatory, and antidepressant effects via its Gi protein-coupled receptor subtype 4 (SST(4)) without endocrine actions. SST(4) is suggested to be a unique novel drug target for chronic neuropathic pai...

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Autores principales: Kecskés, Angéla, Pohóczky, Krisztina, Kecskés, Miklós, Varga, Zoltán V., Kormos, Viktória, Szőke, Éva, Henn-Mike, Nóra, Fehér, Máté, Kun, József, Gyenesei, Attila, Renner, Éva, Palkovits, Miklós, Ferdinandy, Péter, Ábrahám, István M., Gaszner, Balázs, Helyes, Zsuzsanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589422/
https://www.ncbi.nlm.nih.gov/pubmed/33096776
http://dx.doi.org/10.3390/ijms21207788
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author Kecskés, Angéla
Pohóczky, Krisztina
Kecskés, Miklós
Varga, Zoltán V.
Kormos, Viktória
Szőke, Éva
Henn-Mike, Nóra
Fehér, Máté
Kun, József
Gyenesei, Attila
Renner, Éva
Palkovits, Miklós
Ferdinandy, Péter
Ábrahám, István M.
Gaszner, Balázs
Helyes, Zsuzsanna
author_facet Kecskés, Angéla
Pohóczky, Krisztina
Kecskés, Miklós
Varga, Zoltán V.
Kormos, Viktória
Szőke, Éva
Henn-Mike, Nóra
Fehér, Máté
Kun, József
Gyenesei, Attila
Renner, Éva
Palkovits, Miklós
Ferdinandy, Péter
Ábrahám, István M.
Gaszner, Balázs
Helyes, Zsuzsanna
author_sort Kecskés, Angéla
collection PubMed
description Somatostatin is an important mood and pain-regulating neuropeptide, which exerts analgesic, anti-inflammatory, and antidepressant effects via its Gi protein-coupled receptor subtype 4 (SST(4)) without endocrine actions. SST(4) is suggested to be a unique novel drug target for chronic neuropathic pain, and depression, as a common comorbidity. However, its neuronal expression and cellular mechanism are poorly understood. Therefore, our goals were (i) to elucidate the expression pattern of Sstr4/SSTR4 mRNA, (ii) to characterize neurochemically, and (iii) electrophysiologically the Sstr4/SSTR4-expressing neuronal populations in the mouse and human brains. Here, we describe SST(4) expression pattern in the nuclei of the mouse nociceptive and anti-nociceptive pathways as well as in human brain regions, and provide neurochemical and electrophysiological characterization of the SST(4)-expressing neurons. Intense or moderate SST(4) expression was demonstrated predominantly in glutamatergic neurons in the major components of the pain matrix mostly also involved in mood regulation. The SST(4) agonist J-2156 significantly decreased the firing rate of layer V pyramidal neurons by augmenting the depolarization-activated, non-inactivating K(+) current (M-current) leading to remarkable inhibition. These are the first translational results explaining the mechanisms of action of SST(4) agonists as novel analgesic and antidepressant candidates.
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spelling pubmed-75894222020-10-29 Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains Kecskés, Angéla Pohóczky, Krisztina Kecskés, Miklós Varga, Zoltán V. Kormos, Viktória Szőke, Éva Henn-Mike, Nóra Fehér, Máté Kun, József Gyenesei, Attila Renner, Éva Palkovits, Miklós Ferdinandy, Péter Ábrahám, István M. Gaszner, Balázs Helyes, Zsuzsanna Int J Mol Sci Article Somatostatin is an important mood and pain-regulating neuropeptide, which exerts analgesic, anti-inflammatory, and antidepressant effects via its Gi protein-coupled receptor subtype 4 (SST(4)) without endocrine actions. SST(4) is suggested to be a unique novel drug target for chronic neuropathic pain, and depression, as a common comorbidity. However, its neuronal expression and cellular mechanism are poorly understood. Therefore, our goals were (i) to elucidate the expression pattern of Sstr4/SSTR4 mRNA, (ii) to characterize neurochemically, and (iii) electrophysiologically the Sstr4/SSTR4-expressing neuronal populations in the mouse and human brains. Here, we describe SST(4) expression pattern in the nuclei of the mouse nociceptive and anti-nociceptive pathways as well as in human brain regions, and provide neurochemical and electrophysiological characterization of the SST(4)-expressing neurons. Intense or moderate SST(4) expression was demonstrated predominantly in glutamatergic neurons in the major components of the pain matrix mostly also involved in mood regulation. The SST(4) agonist J-2156 significantly decreased the firing rate of layer V pyramidal neurons by augmenting the depolarization-activated, non-inactivating K(+) current (M-current) leading to remarkable inhibition. These are the first translational results explaining the mechanisms of action of SST(4) agonists as novel analgesic and antidepressant candidates. MDPI 2020-10-21 /pmc/articles/PMC7589422/ /pubmed/33096776 http://dx.doi.org/10.3390/ijms21207788 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kecskés, Angéla
Pohóczky, Krisztina
Kecskés, Miklós
Varga, Zoltán V.
Kormos, Viktória
Szőke, Éva
Henn-Mike, Nóra
Fehér, Máté
Kun, József
Gyenesei, Attila
Renner, Éva
Palkovits, Miklós
Ferdinandy, Péter
Ábrahám, István M.
Gaszner, Balázs
Helyes, Zsuzsanna
Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains
title Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains
title_full Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains
title_fullStr Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains
title_full_unstemmed Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains
title_short Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains
title_sort characterization of neurons expressing the novel analgesic drug target somatostatin receptor 4 in mouse and human brains
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589422/
https://www.ncbi.nlm.nih.gov/pubmed/33096776
http://dx.doi.org/10.3390/ijms21207788
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