Characterization of Neurons Expressing the Novel Analgesic Drug Target Somatostatin Receptor 4 in Mouse and Human Brains
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Kecskes, Angela; Pohoczky, Krisztina; Kecskes, Miklos; Varga, Zoltan V.; Kormos, Viktoria; Szoke, Eva; Henn-Mike, Nora; Feher, Mate; Kun, Jozsef; Gyenesei, Attila; Renner, Eva; Palkovits, Miklos; Ferdinandy, Peter; Abraham, Istvan M.; Gaszner, Balazs; Helyes, Zsuzsanna
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.
The effect of somatostatin analogs and acromegaly on the upper gastrointestinal system
PITUITARY
Authors: Sahin, Serdar; Icli, Tevhide Betul; Durcan, Emre; Sulu, Cem; Ozkaya, Hande Mefkure; Hatemi, Ali Ibrahim; Kadioglu, Pinar
Abstract
Purpose To evaluate the effects of somatostatin analogs and disease activity status on the upper gastrointestinal system in patients with acromegaly. Methods One hundred eighty-one patients with acromegaly were retrospectively assessed. The demographic, biochemical, pathologic, and radiologic data of the patients were evaluated. The upper gastrointestinal endoscopies and endoscopic biopsies were investigated. We divided patients into four groups according to the use of somatostatin analogs, and into two groups according to disease activity. We compared the data of patients between groups A, B, C, and D, and controlled/uncontrolled groups separately. Results Before and in the peri-endoscopic period, 67 and 27 patients were being treated with octreotide long-acting release (LAR) (group A) and lanreotide autogel (group B), respectively. Twenty-one patients used somatostatin analogs, but they were stopped for various reasons before upper gastrointestinal endoscopy (group C), and 66 patients did not use a somatostatin analog (group D). In the peri-endoscopic period, 103 (60%) patients were responsive to medical and/or surgical treatment and 67 (40%) patients were non-responsive. The rate of gastritis was higher in group A than in groups B and D. The incidence of duodenitis and gastric ulcer was much higher in group D. The rate of gastritis was higher in the controlled group compared to the uncontrolled group. Conclusion The study showed that octreotide LAR treatment could be a risk factor in addition to known factors for the development of gastritis in patients with acromegaly.