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Protective Role of the Somatostatin Receptor Subtype 4 in the Indomethacin‐Induced Gastrointestinal Mucosal Injury Model
Author(s) -
Csekő Kata,
Kormos Viktória,
Horváth Ádám,
Sudalina Maria,
Iarushkitalia,
Zelena Dóra,
Filaretova Ludmila,
Helyes Zsuzsanna
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb71
Subject(s) - somatostatin , extravasation , myeloperoxidase , medicine , small intestine , stomach , somatostatin receptor , enteroendocrine cell , endocrinology , neuropeptide y receptor , jejunum , inflammation , receptor , pathology , endocrine system , neuropeptide , hormone
Since gastrointestinal ulceration is still associated with high mortality despite advancements in the endoscopic and pharmacological management, precise understanding of the mucosal defensive and protective mechanisms is important. The neuropeptide somatostatin is present in the endocrine cells and sensory nerves, is analogues were shown to reduce mucosal blood flow, pepsin and gastric acid secretion. Its endocrine functions are mediated by the receptors sst 2,3,5 , and our group discovered that the anti‐inflammatory and analgesic actions are exerted via the sst 4 receptor. Sst 4 agonists are preclinically tested as novel drug candidates in theses areas. Therefore, we investigated the role of sst 4 in gastrointestinal injury. Sst 4 gene‐deleted (sst 4 −/− ) mice and wildtype counterparts (sst 4 +/+ ) were treated s.c. with 35 mg/kg indomethacine (IDM) or its vehicle. Macroscopic and microscopic mucosal lesions in the stomach and small intestine were evaluated by the ImageJ program and semiquantitative histopathological scoring after 4 and 48 h, respectively. Small intestinal length, thymus, adrenal glands, spleen weight and plasma glucose levels were measured. Neutrophil myeloperoxidase (MPO) activity and plasma extravasation were measured by bioluminescent/fluorescent ex vivo imaging after 24 h. Macroscopic lesion area and MPO activity in the gastric mucosa were significantly greater in IDM‐treated sst 4 −/− mice than in wildtypes 4 h and 24 h after IDM administration, respectively. Similar tendency was observed in the duodenum and jejunum even after 48 h. However, IDM did not induce mucosal plasma extravasation in either group at the 24 h timepoint. Thymus weight was significantly less in sst 4 −/− mice than in sst 4 +/+ ones. Histopathological scores, small intestinal length, adrenal and spleen weight, and plasma glucose level were not altered by the sst 4 deletion. These results provide evidence for a protective role of the sst 4 receptor against chemical injury‐induced gastrointestinal mucosal damage. This shows the safety of sst 4 agonist drug candidates in the gastrointestinal tract, and even highlights their potential use for gastroprotective indication. Support or Funding Information GINOP‐2.3.2‐15‐2016‐00050 – PEPSYS, GINOP‐2.3.2 STAY ALIVE, EFOP‐3.6.2‐16‐2017‐00008, ÚNKP‐18‐3 New National Excellence Program of the Ministry of Human Capacities This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .