Characteristics of gastrin controlled ECL cell specific gene expression

BACKGROUND: The ECL cells are histamine-producing endocrine cells in the oxyntic mucosa that synthesize and secrete proteins and peptides. They are the primary target for gastrin and mediate the control of gastrin on acid secretion and oxyntic mucosal growth. Knowledge of the molecular biology of the ECL cell is therefore important for understanding gastric physiology. Accordingly, we wanted to identify genes that are characteristically expressed in the ECL cells and controlled by gastrin. METHODS: Using Affymetrix GeneChips, RNA expression profiles were generated from ECL cells isolated by counterflow elutriation from hyper- or hypogastrinemic rats. Contamination from non-endocrine cells was eliminated by subtraction of the expression profiles of the fundic and antral mucosa. RESULTS: The expression of 365 genes was ECL cell characteristic. Gastrin was found to control the expression of 120 which could be divided into two major groups depending on the known or anticipated biological function of the encoded protein: genes encoding proteins involved in the secretory process and genes encoding proteins needed to generate energy for secretion. Interestingly, gastrin stimulation also increased ECL cells expression of anti-apoptotic genes. CONCLUSION: The ECL cell specific expression profile is reminiscent of that of neurons and other endocrine cells exhibiting high expression of genes encoding proteins involved in the synthesis, storage and secretion of neuropeptides or peptide hormones. Gastrin regulated the expression of one third of these genes and is thus involved in the control of secretion from the ECL cells.     

P53、PCNA、CA724、胃泌素17 及幽门螺杆菌抗体联合检测在萎缩性胃炎与早期胃癌鉴别中的应用价值

目的探讨P53、增殖细胞核抗原(PCNA)、糖类抗原724(CA724)、胃泌素17(G-17)及幽门螺杆菌(HP-IgG)抗体联合检测在萎缩性胃炎与早期胃癌鉴别中的应用价值。方法选取2017年11月至2018年11月在湖南省人民医院(湖南师范大学第一附属医院)消化科行胃镜检查的186例患者作为研究对象,根据病理诊断结果分为正常对照组(50例),萎缩性胃炎组(76例),胃癌组(60例)。采用免疫组化检测P53、PCNA的表达情况;采用电化学发光免疫分析法检测血清CA724水平;采用酶联免疫法检测血清G-17水平;采用胶体金法定性检测HP-IgG抗体表达。分析各指标对萎缩性胃炎与早期胃癌鉴别的价值。结果胃癌组患者P53、PCNA阳性率高于萎缩性胃炎组和对照组(均P0.05)。胃癌组、萎缩性胃炎组患者HP-IgG阳性率明显高于对照组(均P0.05),同时胃癌组HP-IgG阳性率高于萎缩性胃炎组(均P0.05)。胃癌组患者血清CA724水平明显高于对照组和萎缩性胃炎组(P0.05)。胃癌组患者血清G-17水平高于萎缩性胃炎组和对照组(均P0.05),同时萎缩性胃炎组血清G-17水平明显低于对照组(P0.05)。HP-IgG抗体阳性患者P53、PCNA阳性率以及血清CA724、G-17水平均高于HP-IgG抗体阴性患者(均P0.05)。CA724预测胃癌的AUC为0.815,截断值为33.57 U/mL,灵敏度为70.00%,特异性为83.33%。G-17预测胃癌的AUC为0.847,截断值为15.36 U/mL,灵敏度为80.00%,特异性为85.71%。各指标联合检测胃癌的灵敏度、特异性、阳性预测值、阴性预测值及准确度均高于单指标检测。结论胃癌患者P53、PCNA、HP-IgG抗体阳性率较高,血清CA724、G-17水平升高,而萎缩性胃炎患者血清G-17水平降低,可作为萎缩性胃炎与早期胃癌的鉴别指标。各指标联合检测可提高对胃癌的诊断价值。     

胃癌前病变患者胃蛋白酶原、促胃液素-17水平变化及幽门螺杆菌感染情况

目的研究胃癌前病变患者胃蛋白酶原、促胃液素-17及幽门螺杆菌(H.pylori)感染情况变化。方法试验组患者选取2017年8月至2018年8月间于我院进行治疗的100例胃癌前病变患者,对照组选取来我院体检中心进行体检的健康人员60例,对比两组人群胃蛋白酶原、促胃液素-17及H.pylori感染情况变化。结果试验组PGI(57.45±11.52)、PGII(8.65±1.75)、PGR(5.89±1.26)和促胃液素-17(8.05±1.45)水平显著低于对照组(均P<0.05);试验组H.pylori感染率81.00%显著高于对照组感染率41.67%,差异有统计学意义(P<0.05)。结论胃癌前病变患者PGI、PGII、PGR和促胃液素-17水平较低,并且H.pylori感染率高,患病与H.pylori感染有一定关系,胃蛋白酶原、促胃液素-17和H.pylori感染率对胃癌前病变临床诊断有重要作用,能够作为胃癌前病变患者筛查参考指标。     

越鞠丸联合子午流注开穴疗法对功能性消化不良伴焦虑抑郁患者血清胃泌素、胃蛋白酶原的影响

摘要 目的：探讨越鞠丸联合子午流注开穴疗法治疗功能性消化不良（FD）伴焦虑抑郁的疗效及对血清胃泌素、胃蛋白酶原的影响。方法：选取2017年7月~2020年7月期间南京市第一医院和首都医科大学附属北京中医医院收治的150例FD伴焦虑抑郁患者,以随机数字表法分为对照组（n=75,常规西医治疗）和研究组（n=75,对照组基础上给予越鞠丸联合子午流注开穴疗法治疗）。疗程均为4周。对比两组治疗4周后的临床疗效,对比两组治疗前、治疗4周后的中医证候积分、焦虑抑郁情况、血清胃泌素和胃蛋白酶原水平。结果：对照组的临床总有效率为76.00%（57/75）,低于研究组的92.00%（69/75）（P<0.05）。治疗4周后,两组主证（脘腹胀满、胃痛、食欲不振）、次证（胁肋胀痛、嗳气泛酸、恶心呕吐、烦躁太息、神疲乏力、口苔黏腻、大便稀溏）积分均降低,且研究组较对照组低（P<0.05）。治疗4周后,两组Zung抑郁自评量表（SDS）、Zung焦虑自评量表（SAS）评分均降低,且研究组较对照组低（P<0.05）。治疗4周后,两组血清胃泌素、胃蛋白酶原1、胃蛋白酶原2水平均升高,且研究组较对照组高（P<0.05）。结论：采用子午流注开穴疗法联合越鞠丸治疗FD伴焦虑抑郁患者,可有效改善患者焦虑抑郁状态和临床症状,提高血清胃泌素和胃蛋白酶原水平,明显提升临床疗效。     

Sulfated gastrin stimulates ghrelin and growth hormone release but inhibits insulin secretion in cattle

This study was designed to determine the effects of gastrin on the circulating levels of ghrelin, growth hormone (GH), insulin, glucagon and glucose in ruminants. Two experiments were done in eight Holstein steers. Animals were randomly assigned to receive intravenous bolus injections: (1) 0.1% bovine serum albumin in saline as vehicle, 0.8, 4.0 and 20.0 μg/kg body weight (BW) of bovine sulfated gastrin-34; (2) vehicle, 0.53 μg/kg BW of bovine sulfated gastrin-17 alone or combined with 20.0 μg/kg BW of [d-Lys³]-GHRP-6, the selective antagonist of GHS-R1a. Blood samples were collected from −10 to 150 min relative to injection time. Concentrations of acyl and total ghrelin in response to gastrin-34 injection were significantly increased in a dose-dependent manner. Concentrations of GH were also markedly elevated by gastrin-34 injection; however, the effect of 20.0 μg/kg was weaker than that of 4.0 μg/kg. The three doses of gastrin-34 equally decreased insulin levels within 15 min and maintained the level until the time of last sampling. Gastrin-34 had no effect (P > 0.05) on the levels of glucagon and glucose. Levels of acyl ghrelin increased after administration of gastrin-17 alone or combined with [d-Lys³]-GHRP-6; however, [d-Lys³]-GHRP-6 did not block the elevation of GH by gastrin-17. The present results indicate that sulfated gastrin stimulates both ghrelin and GH release, but the GHS-R1a may not contribute to the release of GH by gastrin. Moreover, sulfated gastrin seems to indirectly maintain the homeostasis of blood glucose through the down-regulation of insulin in ruminants.     

Distribution and projections of neurons with immunoreactivity for both gastrin-releasing peptide and bombesin in the guinea-pig small intestine

Summary Bombesin-like and gastrin-releasing peptide (GRP)-like immunoreactivities were localized in nerves of the guinea-pig small intestine and celiac ganglion with the use of antibodies raised against the synthetic peptides. The anti-bombesin serum (preincubated to avoid cross reactivity with substance P) and the anti-GRP serum revealed the same population of neurons. Preincubation of the antibombesin serum with bombesin abolished the immunoreactivity in nerves while absorption of the anti-GRP serum with either bombesin or the 14–27 C-terminal of GRP only reduced the immunoreactivity. The immunoreactivity was abolished by incubation with GRP 1–27.Immunoreactive nerves were found in the myenteric plexus, circular muscle, submucous plexus and in the celiac ganglion. Faintly reactive nerve cell bodies were found in the myenteric ganglia (3.2% of all neurons) but not in submucous ganglia. After all ascending and descending pathways in the myenteric plexus had been cut, reactive terminals disappeared in the myenteric plexus, circular muscle (including the deep muscular plexus) and the submucous plexus on the anal side. After the mesenteric nerves were cut no changes were observed in the intestinal wall but the reactive fibres in celiac ganglia disappeared. It is deduced that GRP/bombesin-immunoreactive nerve cell bodies in myenteric ganglia project from the myenteric plexus to other myenteric ganglia situated further anally (average length 12 mm), anally to the circular muscle (average length 9 mm), anally to submucous ganglia (average length 13 mm) and external to the intestine to the celiac ganglia.It is concluded that the GRP/bombesin-reactive neurons in the intestinal wall represent a distinct population of enteric neurons likely to be involved in controlling motility and in the coordination of other intestinal functions.     

Evidence for central neuropeptidergic control of rumination in sheep

Effects of intracerebroventricular (ICV) vs. intravenous (IV) administration of tetragastrin, pentagastrin, CCK₈ and gastrin 17 on rumination were investigated in conscious sheep. Administered at 26 pmoles/kg ICV both tetra and pentagastrin induced a premature short (15–27 min) period of rumination only $\text{24±7}$ and $\text{23±9}$ min after food distribution in place of $\text{112±44}$ min in controls. Similar but less pronounced effects were observed for ICV administration of an equimolar dose of gastrin 17 whereas CCK₈ did not promote an early peciod of rumination despite its anorectic effects. Administered intravenously tetra and pentagastrin but not gastrin 17 caused early rumination only for 10 times higher doses. It is concluded that gastrin 17 and its C-terminal tetrapeptide may play a physiological role in the central control of rumination in sheep.     

Participation of the microtubular-microfilamentous system on intracellular Ca transport and acid secretion in dispersed parietal cells

Biphasic responses of amino[¹⁴C]pyrine accumulation and oxygen consumption were registered by gastrin stimulation in dispersed parietal cells from guinea pig gastric mucosa, and this was mimicked with the calcium ionophore A23187. The characteristics of these phases (first phase and second phase) were distinguished by the differences in the requirements of extracellular Ca²⁺. The first phase evoked by gastrin or ionophore A23187 was independent of extracellular Ca²⁺, whereas the second phase was not. In the first phase, fluorescence of a cytosolic Ca²⁺ indicator (quin2-AM) increased with the stimulation of ionophore A23187 and carbamylcholine chloride in the presence of extracellular Ca²⁺. In addition, an increase in cytosolic Ca²⁺ induced by ionophore A23187, but not by carbamylcholine chloride was also observed in the absence of extracellular Ca²⁺, suggesting that Ca²⁺ pool(s) in parietal cells might be present in the intracellular organelle. Cytochalasin B and colchicine, but not oligomycin, could eliminate this cytosolic Ca²⁺ increase induced by A23187 in a Ca²⁺-free medium. On the other hand, in a Ca²⁺-free medium, addition of ATP after pretreatment with digitonin could diminish the cytosolic Ca²⁺ increase brought about by A23187. This was also observed with oligomycin-treated cells, but not with cytochalasin B-treated cells. Similarly, subcellular fractionation of a parietal cell which had been pretreated with cytochalasin B or colchicine in an intact cell system reduced the rate of ATP-dependent Ca²⁺ uptake. These observations indicate that intracellular Ca²⁺ transport in dispersed parietal cells may be regulated by the microtubular-microfilamentous system. In conclusion, this study demonstrates the possibility of the existence of intracellular Ca²⁺ transport mediated by gastrin or ionophore A23187 and regulated by the microtubular-microfilamentous system in parietal cells.