十二指肠粘膜HCO3-的分泌具有维持刷状缘碱性微环境、保护粘膜免受酸损伤的作用。临床发现胃十二指肠溃疡在多巴胺（DA）系统功能减退者（如帕金森病）发病率高，亢进者（如精神分裂症）发病率明显降低。提示DA具有胃肠粘膜保护作用。胃粘膜可以合成DA，DA受体广泛分布于十二指肠粘膜，但胃DA能否通过幽门刺激十二指肠腔面膜DA受体引起HCO3-分泌、其作用的受体亚型、信号通路和相关膜通道/转运体等并不清楚。本研究采用在体胃灌流、高压液相和放免等方法测定胃液DA含量；采用免疫组化、分子生物学、酶联免疫和激光切割等技术对十二指肠粘膜DA受体、信号通路中关键蛋白、膜转运体和通道等进行定位和定量检测；采用实时pH滴定、胞内pH和钙敏感荧光探针、基因干扰结合相关动物模型等研究DA对HCO3-分泌的影响。为胃源性DA调节十二指肠HCO3-分泌的机制、帕金森病胃十二指肠溃疡高发病率的病因提供理论与实验依据。

Duodenal bicarbonate secretion plays a vital role in maintaining the alkaline microenvironment of brush border and protecting mucosa from H+ in gastric juice. Clinical research suggests that patients with dopaminergic dysfuction (such as Parkinson's disease) suffers from a higer incidence of gastroduodenal ulcer, while a lower incidence has been reported in the patients with the dopaminergic hyperfunction, which indicates that dopamine might contribute to the preservation of gastrointestinal mucosa. Previous studies have shown that gastric parietal cells can synthesis dopamine, and dopamine receptors are widespreadly distributed in the duodenal mucosa. However, it remains unknown whether gastric dopamine can enter duodenum via pylorus and stimulate duodenal bicarbonate secretion by combining with the dopamine receptors on the luminal membrane. It is also worthwhile to find out the subtypes of DA receptors, key protiens in signaling pathways and the channels or transporters of cell membrane involved in this process. To discover the mechanism underlying the dopamine regulating duodenal bicarbonate secretion, the following methods will be employied. In vivo stomach perfusion, radioimmunoassay (RIA) and high pressure liquid (HPLC) etc.will be used to measure the content of DA in gastric juice. The location and quantitative detecting techniques including immunohistochemistry, molecularbiology, enzyme linked immunosorbent assay and laser cutting will be used to determine the expression and alterations of dopamine receptors, key protiens in signaling pathways, and relative membrane channels or transporters in duodenal epithelia. In addition, the real-time pH titration, intracellular pH measurement, calcium-sensitive fluorescent probe, dopamine receptor RNA inteference and relevant animal models with altered endogenous DA will be applied. The present study will provide some theoretical and experimental information for the mechanism underlying the regulation of gastric DA on the duodenal HCO3- secretion and the cause of the high ulcer incidence in PD condition.