REAL

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

Kecskés, Angéla and Pohóczky, Krisztina and Kecskés, Miklós and Varga, Zoltan V. and Kormos, Viktória and Szőke, Éva and Henn-Mike, Nóra and Fehér, Máté and Kun, József and Gyenesei, Attila and Renner, Éva and Palkovits, Miklós and Ferdinandy, Péter and Ábrahám, István M. and Gaszner, Balázs and Helyes, Zsuzsanna (2020) Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (20). No.-7788. ISSN 1661-6596

[img]
Preview
Text
SSTR4_ijms-21-07788-v2.pdf

Download (7MB) | Preview

Abstract

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 (SST4) without endocrine actions. SST4 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 SST4 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 SST4-expressing neurons. Intense or moderate SST4 expression was demonstrated predominantly in glutamatergic neurons in the major components of the pain matrix mostly also involved in mood regulation. The SST4 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 SST4 agonists as novel analgesic and antidepressant candidates.

Item Type: Article
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában > R850-854 Experimental medicine / kisérleti orvostudomány
Depositing User: Dr. Zoltán Varga
Date Deposited: 24 Sep 2021 13:04
Last Modified: 03 Apr 2023 07:22
URI: http://real.mtak.hu/id/eprint/130387

Actions (login required)

Edit Item Edit Item