Beeinflussung gastrointestinaler Motilität und Entzündung durch atypische Cannabinoide - Einfluss des GPR55-Cannabinoidrezeptors

功能性胃肠疾病是患者寻求医疗帮助的常见原因，并与生活质量受损有关。消化不良和肠易激综合征的患病率在10%到15%之间。这些功能障碍的药物治疗选择是有限的，主要由不同的对症治疗方法组成。有趣的是，功能性胃肠疾病在女性中更常见，至少女性更频繁地寻求医疗建议。GPR30受体是最近报道的一种受体，它被证明是雌激素的可能靶点。这种受体的定位和功能尚不清楚。本项目拟研究GPR30受体是否定位于胃肠道，如果定位于胃肠道，确定这些受体的功能意义。我们的翻译方法包括小鼠的体外和体内研究以及人体组织的体外研究。利用PCR和免疫组织化学技术，我们的目标是在胃肠道中定位GPR30，然后进行体外药理学和电生理实验，这将使我们能够评论GPR30在胃肠道功能控制中的可能功能相关性。在这些实验的基础上，我们打算在模拟肠易激综合征症状的体内模型中进行实验，以确定GPR30对胃肠道分泌、运动、腹泻和内脏感觉的可能作用。选定的体外实验和染色将在人体组织中重现，以便讨论在人体背景下所做的观察结果，并促进未来更有针对性地研究功能性胃肠道疾病背景下的GPR30受体。

Functional gastrointestinal disorders are frequent reasons for patients to seek medical help and are associated with impaired quality of life. Prevalence of dyspepsia and irritable bowel syndrome range from 10 to 15 %. Drug treatment options of these functional disorders are limited and mostly consist of different symptomatic therapeutic approaches. Interestingly functional gastrointestinal disorders are more frequent in females, at least females more frequently seek medical advice.The GPR30 receptor is a recently reported receptor which was shown to be a possible target for estrogens. Localisation and function of this receptor are unknown. The suggested project wants to investigate whether GPR30 receptors are localized in the gastrointestinal tract and if so, to identify the functional meaning of these receptors. Our translational approach comprises in vitro and in vivo studies in mice and in vitro studies in human tissue. Employing PCR and immunohistochemistry we aim to localize GPR 30 in the gastrointestinal tract followed by in vitro pharmacological and electrophysiological experiments that will allow us to comment on the possible functional relevance of GPR30 in the control of gastrointestinal function. Building on these experiments we intend to perform experiments in in vivo models mimicking symptoms of irritable bowel syndrome in order to identify possible GPR30 actions on gastrointestinal secretion, motility, diarrhoea and visceral sensation. Selected in vitro experiments and stainings will be reproduced in human tissues to allow discussion of the observations made in the context of human and to facilitate future more targeted investigation of GPR30 receptor in the context of functional gastrointestinal disorders.