The Effect of Propranolol and Phentolamine on Serum Gastrin Concentration in Response to Respiratory Acidosis in Normal Man

Abstract. Serum gastrin concentration and basal acid secretion were studied in normal subjects under the influence of respiratory acidosis induced by CO2 rebreathing. During the intragastric instillation of 100 ml/h 0. 5 M bicarbonate a significant increase of gastrinaemia from 130 to 158 pg/ml (p < 0. 01) occurred in ten subjects during respiratory acidosis (pCO₂ 62 torr, pH 7. 25). Under, the intragastric instillation of 100 ml/h 0. 1 N HC1 the rise of gastrin concentration in response to CO2 rebreathing (pC02 68 torr, pH 7. 20) was not significant. The relationship between the decrease of pH and the increase of the gastrin concentration was shifted in the direction of a greater systemic acidosis compared to the results performed in the presence of a neutral intragastric pH. 50 μg/kg propranolol intravenously produced a decrease of gastrin concentrations from 145 to 127 pg/ml (p < 0. 01) and a total suppression of hyper-gastrinaemia in respons'e to CO₂ rebreathing, suggesting activation of beta-cell receptors in respiratory acidosis. The infusion of phentolamine in a dose of 0. 6 to 1. 8 mg/min. resulted in a rise of gastrin concentration from 140 to 165 pg/ml (p < 0. 01) which was not further elevated during respiratory acidosis. The basal acid secretion showed a significant rise in response to CO2 rebreathing, which was abolished by the administration of propranolol.     

Nonpeptide gastrin releasing peptide receptor antagonists inhibit the proliferation of lung cancer cells

The ability of nonpeptide antagonists to interact with gastrin releasing peptide receptors on lung cancer cells was investigated. PD176252 (3-(1H-Indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide) and PD168368 (3-(1H-Indol-3-yl)-2-methyl-2-[3(4-nitro-phenyl)-ureido]-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide) inhibited specific 125I-gastrin releasing peptide binding to NCI-H1299 cells with IC50 values of 20 and 1500 nM, respectively. Similar binding results were obtained using NCI-H157, H345 and N592 human lung cancer cells. PD176252 inhibited the ability of 1 nM bombesin to cause elevation of cytosolic calcium in Fura-2 loaded NCI-H345 or H1299 cells, whereas it had no effect on basal cytosolic calcium. PD176252 antagonized the ability of 10 nM bombesin to cause elevation of c-fos mRNA in NCI-H1299 cells. Also, PD176252 inhibited the ability of 100 nM bombesin to cause tyrosine phosphorylation of focal adhesion kinase in NCI-H1299 cells. Using a [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay, PD176252 was more potent than PD168368 at inhibiting NCI-H1299 proliferation. Also, 1 microM PD176252 significantly inhibited lung cancer colony number in vitro. PD176252 in a dose-dependent manner inhibited NCI-H1299 xenograft growth in nude mice in vivo. These results indicate that PD176252 is a gastrin releasing peptide receptor antagonist, which inhibits the proliferation of lung cancer cells.     

冒癌表达胃泌素受体的特征

目的 研究胃癌表达胃泌素受体(gastrin receptor,GR)的特征及意义。 方法 应用受体的放射配基结合分析法测定34例胃癌标本GR含量及其亲和力,并比较胃癌表达的GR与其部位、分期、分级、胃癌细胞DNA含量、邻近正常胃粘膜的GR及患者生存期的关系。 结果 34例胃癌组织中,16例(47.1％)胃癌GR阳性,其中14例(41.2％)表达高亲和力GR,2例表达低亲和力GR;在高亲和力GR中,9例表达高含量GR(平均含量39.5±14.4 fmol/mg蛋白),5例表达低含量GR(平均含量6.0±2.8 fmol/mg蛋白)。胃体癌(77.8％)和贲门癌(50％)较胃窦癌(20.1％)更易于表达高亲和力GR。相同部位的胃癌及邻近正常粘膜表达GR是一致的,但胃癌表达的胃泌素受体含量(39.5±14.4 fmol/mg蛋白)高于粘膜(26.1±16.6 fmol/mg蛋白)。Ⅲ、Ⅳ期胃癌表达高亲和力GR的比例(13/24)明显高于Ⅰ、Ⅱ期胃癌(1/10)。胃癌表达的GR与癌细胞的分级无关。随访23～61月发现,对于Ⅲ、Ⅳ期胃癌患者,13例表达高亲和力GR的胃癌,有11例死亡;而11例低亲和力GR或GR阴性的胃癌,仅有4例死亡。 结论 GR在胃癌自分泌生长过程中也是一个重要的因素;GR有利于预测患者的预后及指导GR拮抗剂的应用。     

Cow's milk intolerance with melena

The clinical features, the results of gastric secretory function tests, and the duodenojejunal morphology of six infants (aged 0.42–1.23 years) with anemia and melena considered to be due to latent cow's milk intolerance (LCMI) were compared with the findings in nine infants (aged 0.19–0.87 years) with cow's milk-induced malabsorption (CMI). The infants with LCMI had a short period of breast feeding, normal weight gain without symptoms of malabsorption, and no atopic history. The maximal acid secretion was decreased (P<0.01) and the concentration of fasting serum gastrin raised (P<0.01) compared with the controls. Gastric biopsy revealed epithelial degeneration in three and erosion in one out of four samples.The duodenojejunal biopsy revealed slight changes in two samples, the others being normal. The number of eosinophils was increased in four out of six biopsies. Although the number of intraepithelial lymphocytes was increased in LCMI the rise was not as significant as in children with CMI (P<0.05).We conclude from our results that LCMI seems to be a separate clinical entity. The determination of fasting serum gastrin, maximal gastric acid secretion and intraepithelial lymphocytes on duodenojejunal biopsy appear to be helpful in making the diagnosis.     

Immunohistochemistry and morphometry of gastrin cells in the rat pyloric antrum during starvation

Summary The gastrin cells (G cells) in the rat pyloric antrum after 7, 14, 21 and 28 days of starvation were investigated by immunohistochemistry and electron microscopy. In the peroxidase anti-peroxidase method for light microscopy, gastrin immunoreactive cells during starvation markedly decreased in number and size. Quantitative electron microscopy revealed that during starvation the number of electron-lucent granules were greatly reduced, but the number of electron-dense granules increased; the number of intermediate granules were not remarkably changed in G cells. These results may suggest that the synthesis of gastrin and granule maturation were greatly inhibited during long-term starvation.     

泰胃美用于围麻醉期呕吐误吸的防治（附30例分析）

目的　通过测定静脉注射泰胃美前后胃液 p H及血清胃泌素含量 ,探讨泰胃美对围麻醉期呕吐、误吸的防治作用。方法　选择胆囊切除手术 30例 ,随机分成实验组和对照组各 15例 ,实验组于全麻诱导前 30分钟静脉注射泰胃美 2 0 0 mg,对照组静脉注射生理盐水 2 ml。全部病人采用气静 +吸入复合麻醉 ,分别于麻醉诱导前、后 30分钟 ,抽取静脉血 2 .0 ml测定胃泌素含量及吸取胃液 5 .0 ml测定 p H值。结果　应用泰胃美前胃液 p H值为 2 .8± 0 .5 ,而用泰胃美后 30分钟胃液 p H上升为 4.5± 0 .6 (P<0 .0 1)。应用泰胃美前血清胃泌素含量为 138.5 6± 5 6 .38(pg/ ml) ,而用泰胃美 30分钟后为 111.6 0± 45 .6 (P<0 .0 1)。结论　应用泰胃美可使胃酸和胃泌素分泌下降 ,胃液 p H值迅速增高 ,可达 4.0以上。对预防呕吐、误吸及误吸性肺炎、呼吸衰竭具有一定意义     

大鼠实验性胃溃疡自愈期间胃窦粘膜G、D细胞变化的免疫组织化学研究

本实验用成年雄性Wistar大鼠53只,分为溃疡组、盐水对照组和正常对照组。在手术后4、10,14、21及28天分批取材。用Sternberger PAP法进行免疫组织化学染色,分别显示胃窦粘膜胃泌素细胞(G细胞)和生长抑素细胞(D细胞),观察大鼠实验性胃溃疡自愈期间,G和D细胞的形态变化,并进行了细胞计数和统计学分析。本文结果表示,溃疡组G细胞数量在术后10至14天明显增多(P<0.01),21、28天趋于减少,但仍高于对照组。有些G细胞排列成群,密集呈明显带状。正常时G细胞分布在幽门腺的中、下1/3处,而溃疡组可见有些G细胞分布在腺的上部。D细胞数量仅在术后10天增多(P<0.01),与正常对照组相比差异显著。用免疫组织化学双重染色法,可见G细胞和D细胞之间存在着形态上的接触。溃疡自愈期间,G/D细胞比值未见明显改变。本实验结果提示,胃窦粘膜局部G、D细胞的变化和大鼠实验性胃溃疡自愈修复之间有着一定的联系。     

Bombesin microinfusion into the paraventricular nucleus suppresses gastric acid secretion in the rat

Bombesin is a particularly potent inhibitor of gastric acid secretion when injected intracisternally in the rat. Because bombesin-like immunoreactivity is found in several forebrain regions implicated in gut regulation, the ability of bombesin to affect gastric secretion was tested in these areas by direct microinfusion. Bombesin significantly and dose-relatedly suppressed gastric acid secretion when it was infused into the hypothalamic paraventricular nucleus. Bombesin microinfusion into the ventromedial or lateral hypothalamic areas, or the caudate-putamen, had no significant effect. A further experiment using glass micropipets showed that back-diffusion of bombesin along the cannula track to a distant site of action was unlikely to account for the results obtained, and provided further evidence that the active site is limited to the paraventricular nucleus and possibly the ventralmost nucleus reuniens. The results suggest that the bombesin receptors and immunoreactive terminals previously identified in this region may be involved in the central regulation of gastric secretion.     

Role of circulating catecholamines in the control of pancreatic polypeptide and gastrin release

The influence of circulating catecholamines on the release of pancreatic polypeptide (PP) and gastrin was studied in volunteers. Physical exercise increased plasma epinephrine by 374 +/- 123% and plasma norepinephrine by 167 +/- 30%, but plasma PP concentrations remained unchanged during standardized bicycle ergometry. Immediately after cessation of exercise catecholamine levels decreased rapidly, whereas PP concentrations increased by 55%. In a second series, epinephrine infusion (5, 25, and 75 ng.kg-1.min-1) increased epinephrine levels by 38 +/- 12, 331 +/- 69, and 1229 +/- 131%, respectively, whilst norepinephrine was unaffected. Neither during nor after catecholamine infusion PP secretion was affected. Gastrin release increased by a maximum of 85 +/- 38% (at epinephrine 75 ng.kg-1.min-1). It is concluded, that (1) changes in circulating adrenaline do not significantly influence PP secretion in man; (2) the PP increase immediately following physical exercise cannot be attributed to a rapid fall of catecholamine levels; (3) endogenous catecholamines are of minor importance in the control of gastrin secretion.     

轮状病毒性肠炎患儿空腹血清胃泌素胃动素水平的研究

目的探讨轮状病毒性肠炎患儿空腹血清胃泌素、胃动素水平的改变.方法用放射免疫分析法分别测定45例婴幼儿轮状病毒性肠炎和16例健康对照者空腹血清胃泌素、胃动素的浓度.结果婴幼儿轮状病毒性肠炎急性期空腹血清胃泌素、胃动素浓度高于恢复期及对照组,差异有显著性意义,p＜0.01.结论胃泌素、胃动素可能参与了轮状病毒性肠炎的发病机制.