Activation of dopamine D2 receptor promotes pepsinogen secretion by suppressing somatostatin release from the mouse gastric mucosa
Activation of dopamine D2 receptor promotes pepsinogen secretion by suppressing somatostatin release from the mouse gastric mucosa
复制标题
多巴胺 D2 受体的激活通过抑制小鼠胃粘膜生长抑素的释放来促进胃蛋白酶原的分泌
DOI：
10.1152/ajpcell.00385.2021
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发表时间：
2022
影响因子：
5.5
通讯作者：
Jin-Xia Zhu
中科院分区：
文献类型：
--
作者：
Xiao-Yu Liu;Li-Fei Zheng;Yan-Yan Fan;Qian-Ying Shen;Yao Qi;Guangwen Li;Qi Sun;Yue Zhang;Xiao-Yan Feng;Jin-Xia Zhu
多巴胺（DA）受体（DR）相关药物的体内给药可调节胃蛋白酶原分泌。然而，随后获得胃胃蛋白酶原分泌主细胞上的DR和生长抑素分泌D细胞上的DA D2受体（D2 R）。本研究旨在进一步研究DA通过主细胞表达的DR或D细胞表达的潜在D2 Rs对胃蛋白酶原分泌的局部作用。为了阐明DR在胃胃蛋白酶原分泌中的调节，进行免疫荧光染色、离体孵育从正常和D2 R-/-小鼠分离的胃粘膜，伴随着使用生化测定或酶联免疫吸附测定测量胃蛋白酶原或生长抑素水平。在小鼠胃粘膜主细胞上观察到D_1 R、D_2 R和D_5 R免疫反应。D2 R-IR广泛分布于D细胞上，从胃体到胃窦。体外孵育结果表明，DA和D1样受体激动剂SKF 38393增加胃蛋白酶原分泌，这是由D1样受体拮抗剂SCH 23390阻断。D2样受体激动剂喹吡罗也能显著促进胃蛋白酶原的分泌，D2样受体拮抗剂舒必利则能阻断DA的促进作用。此外，D2样受体对生长抑素的分泌有抑制作用，而对胃蛋白酶原的分泌无明显影响。此外，D2 R-/-小鼠表现出更低的基础胃蛋白酶原分泌，但显着增加生长抑素释放和胃粘膜中D细胞的数量增加。只有SKF 38393，而不是quinpirole，增加胃蛋白酶原分泌的D2 R-/-小鼠。DA直接通过主细胞上的D1样受体促进胃蛋白酶原分泌，间接通过D2 R介导的生长抑素释放抑制。
In vivo administration of dopamine (DA) receptor (DR)-related drugs modulate gastric pepsinogen secretion. However, DRs on gastric pepsinogen-secreting chief cells and DA D2 receptor (D2R) on somatostatin-secreting D cells were subsequently acquired. In this study, we aimed to further investigate the local effect of DA on gastric pepsinogen secretion through DRs expressed on chief cells or potential D2Rs expressed on D cells. To elucidate the modulation of DRs in gastric pepsinogen secretion, immunofluorescence staining, ex vivo incubation of gastric mucosa isolated from normal and D2R-/- mice were conducted, accompanied by measurements of pepsinogen or somatostatin levels using biochemical assays or enzyme-linked immunosorbent assays. D1R, D2R, and D5R-immunoreactivity (IR) were observed on chief cells in mouse gastric mucosa. D2R-IR was widely distributed on D cells from the corpus to the antrum. Ex vivo incubation results showed that DA and the D1-like receptor agonist SKF38393 increased pepsinogen secretion, which was blocked by the D1-like receptor antagonist SCH23390. However, D2-like receptor agonist quinpirole also significantly increased pepsinogen secretion, and D2-like receptor antagonist sulpiride blocked the promotion of DA. Besides, D2-like receptors exerted an inhibitory effect on somatostatin secretion, in contrast to their effect on pepsinogen secretion. Furthermore, D2R-/- mice showed much lower basal pepsinogen secretion but significantly increased somatostatin release and an increased number of D cells in gastric mucosa. Only SKF38393, not quinpirole, increased pepsinogen secretion in D2R-/- mice. DA promotes gastric pepsinogen secretion directly through D1-like receptors on chief cells and indirectly through D2R-mediated suppression of somatostatin release.