PhD Scientific Days

Poster Presentation: Pharmaceutical

P01: The beneficial effects of the novel α2B/α2C –AR and 5-HT1A agonist cyclomethyline on gastric mucosal integrity and on gastrointestinal motility

Előadó neve

Feher, Agnes

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine, Nagyvárad tér 4. 1089 Budapest, Hungary.

Előadó telefonszáma

(36-1) 210-4416

Előadó e-mail címe

feher.agnes@med.semmelweis-univ.hu

Az előadás címe

The beneficial effects of the novel α2B/α2C –AR and 5-HT1A agonist cyclomethyline on gastric mucosal integrity and on gastrointestinal motility

Szerző(k) neve és munkahelye

Agnes Feher, Viktoria Eva Toth, Bernadette Lazar, Klara Gyires, Zoltan Sandor Zadori
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine, Budapest, Hungary

Szekció

Poster Presentation: Pharmaceutical

Data of the presenter

Doctoral School: Pharmaceutical Sciences
Program: Modern Trends in Pharmaceutical Scientific Research
Supervisor: Zoltan Sandor Zadori
E-mail adress: feher.agnes@med.semmelweis-univ.hu

Text of the abstract

Introduction: It is well-published that α2 –adrenoceptors (AR) play an important role of the regulation of gastrointestinal (GI) tract. The α2A –AR has the predominant role (e.g. it suppresses secretions, peristalsis), but the α2B/α2C –AR subtypes mediate the central gastroprotection. The 5-HT1A inhibits the gastric contractions and also induces gastroprotection. Aims: In this project we aimed to analyze the GI effects of the novel synthesized cyclomethyline, which behaved as α2B/α2C-AR, 5-HT1A receptor agonist and α2A –AR antagonist in in vitro assays. We hypothesized, that cyclomethyline induces very potent gastroprotective effect, because it has an effect on all three receptor subtypes. We also aimed to analyze whether it affects gastric and colonic motility. Methods: We analyzed the effect of cyclomethyline on the ethanol-induced gastric mucosal damage in male Wistar rats, and on the electrical field stimulation (EFS)-induced gastric and colonic contractions in male and female C57BL/6 mice. Results: 1. Intracerebroventricular injection of cyclomethyline reduced significantly and dose-dependently the formation of ethanol-induced mucosal damage. The effect was antagonized by ARC-239, an α2B/2C-AR and 5-HT1A receptor antagonist, but the selective 5-HT1A antagonist S-WAY 100135 had no effect. 2. Cyclomethyline inhibited the EFS-induced gastric and colonic contractions in a concentration-dependent manner. In the case of colonic contractions, the inhibitory effect was significantly reduced in α2B-AR KO mice and by ARC-239 in wild type mice. In the case of gastric contractions only ARC-239 antagonized the effect. Conclusions: Our results confirm that activation of central α2B/2C-ARs induces gastroprotection. Cyclomethyline inhibits colonic motility, which effect is mainly mediated by the α2B-AR subtype, while in case of gastric contractions probably another receptor mediates the inhibitory effect, which is a common target of cyclomethyline and ARC-239.
This work was supported by The ÚNKP-16-3 New National Excellence Program of The Ministry of Human Capacities.

Azonosító

P01

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1035

Authors (legacy)