Secretin dissipates red aridine orange fluoescence from pancreatic duct epithelium

This study was undertaken to elucidate whether duct cells in the pancreas contain acidic cytoplasmic compartments regulated by secretion. Microdissected pancreatic ducts from pigs were examined by acridibe orange (AO) and 2′, 7′-biscarboxyethyl-5(6)-carboxyfluorescein/tetraacetioxymethyl ester (BCECF/AM) epifluorescence microscopy. Estimated cytoplasmic pH using BCECF fluorescence was 7.43pL0.04 and was not changed by altering CO₂ tension in the incubation mdium. The epithelium of acridine orange incbated peripheral interlobular pancreatic ducts exhibited green and fluorescence was sen in resting pancreatic ducts and was greatly accentuated by raising CO₂ in the incubation medium with chloroqyuine or NH₄Cl or the protonophores carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or carbonyl cyanide M-chlorophenylhydrazone (CCCP), leaving uniform gren fluoresence. These findings suggest that pancreatic duct cells contain CO₂-dependent acidic compartments which vanishduring seceatin stimulation and which may be cytoplasmic tubulovesicles.     

Meal-Stimulated Secretin Release in Man: Effect of Acid and Bile

Nine normal subjects were studied before and after intragastric instillation of a liquid meal. Gastric emptying rates of acid and pancreaticobiliary secretions were quantitated by means of a dilution indicator technique. A significant, positive correlation was found between load of acid to the duodenum and the concentration of secretin in plasma. No correlation was found between load of bile acids and plasma secretin. The buffering capacity of gastric contents should bc taken into account when fasting and postprandial period are compared. Plasma secretin concentration remained low during the first postprandial hour. Maximum secretin concentrations and duodenal disappearance rate of acid was observed 1 1/2-2 h after instillation of the meal. In contrast, trypsin output was maximum within 10 min. The data support the concept that in man release of secretin is governed principally by the amount of hydrogen ions emptied into duodenum and indicate the importance of secretin in the late postprandial period, when the acidity of the gastric contents is high.     

Effect of a new cholecystokinin antagonist (FK 480) on gene expression of cholecystokinin and secretin in rat intestine

The effects of a new cholecystokinin (CCK) antagonist (FK 480; 0.1 mg/kg per day given by intragastric administration to rats for 3 days) on the expression of the CCK and secretin genes, plasma CCK immunoreactivity, and CCK content in the intestinal mucosa were examined. FK 480 increased the level of CCK mRNA in the intestine to 1.7 times the level in control rats, but did not affect the level of secretin mRNA. It did not increase plasma CCK immunoreactivity or CCK content in the intestinal mucosa. These results suggest that the ingested FK 480 directly increased CCK mRNA level in the intestine and produced a dissociation between the synthesis and release of CCK.     

Significance of acid amyloglucosidase in sulphonylurea-induced insulin release

Summary The effect of exogenous acid amyloglucosidase on sulphonylurea-induced insulin release was investigated in mice and rats. 1. Pretreatment of mice with acid amyloglucosidase enhanced insulin release induced by the different sulphonylurea derivatives, carbutamide, tolbutamide, glibenclamide, and glibornuride. 2. A dose-response relationship between glibenclamide-induced insulin response and amyloglucosidase dosage covering a 64-fold concentration range was established in mice. 3. Pretreatment of the animals with other macromolecules of similar physiological or chemical properties to acid amyloglucosidase such as-amylase,-glucuronidase and albumin did not influence glibenlamide-induced insulin release. 4. The effect of acid amyloglucosidase pretreatment on insulin release induced by different agents known to affect the islet-cell adenylate cyclase-cyclic AMP system such as secretin, L-isopropylnoradrenaline (L-IPNA), arginine, glibenclamide and 3-isobutyl-1-methylxanthine (IBMX) was tested. It was observed that in animals pretreated with acid amyloglucosidase, insulin release was enhanced when stimulated by glibenclamide, a phosphodiesterase inhibitor, but it was similarly enhanced by arginine, a phosphodiesterase activator. Insulin release induced by secretin, L-IPNA, and IBMX was unaffected. 5. Acid amyloglucosidase pretreatment in rats enhanced plasma immunoreactive insulin levels following glibenclamide injection not only in the peripheral veins but also in the portal vein. 6. Mice fasted for 24 hrs displayed a markedly depressed insulin response to tolbutamide injection. Pretreatment of the fasted animals with acid amyloglucosidase could restore the tolbutamide-induced insulin release to the same level as that recorded in a group of freely fed mice. It is suggested that acid amyloglucosidase plays an important role in insulin secretion induced by sulphonylureas. Most evidence suggests that this effect is exerted within the B-cell although an additional effect on the liver cannot be ruled out.     

11例1型发作性睡病睡眠结构的多导睡眠图分析

目的 探讨1型发作性睡病夜间睡眠的结构特点。 方法 收集1型发作性睡病患者11例和有日间嗜睡但排除相关睡眠疾病的儿童20例。使用多导睡眠监测仪进行整夜(>7 h)连续包括16导脑电图的视频多导睡眠监测(PSG),并于次日进行5次多次小睡潜伏期试验(MSLT)。 结果 与对照组比较,1型发作性睡病组在入睡后觉醒时间占总卧床时间的百分比(WASO%)、非快速眼球运动(NREM)1期睡眠期比例(N1%)增加[17.60(13.10)vs 5.00(12.80),P<0.05;(19.93±12.00)vs(10.12±5.63),P<0.05],入睡潜伏期、快速眼球运动(REM)睡眠潜伏期缩短[5.50 min(11.50 min)vs 13.50 min(22.87 min),P<0.05;(93.50±106.61)min vs(157.47±65.74)min,P<0.05],NREM 3期睡眠期比例(N3%)减少[(17.50±5.60)vs(24.48±7.60),P<0.05]; 但睡眠效率、NREM 2期睡眠期比例(N2%)、REM睡眠期比例(R%)、醒觉指数、睡眠期周期性腿动指数、睡眠呼吸暂停/低通气指数等差别无统计学意义。 结论 1型发作性睡病患者存在夜间睡眠结构紊乱、睡眠片段化现象。     

Secretin is an enterogastrone in humans

We studied in humans the effect of exogenous secretin in a physiological dose on gastric acid secretion stimulated by pentagastrin and postprandial plasma gastrin concentration. Two doses of pentagastrin, 80 and 160 pmol/kg/hr were used to stimulate gastric acid secretion. Secretin in two doses, 2.8 and 5.6 pmol/kg/hr were tried to study the response on stimulated gastric acid secretion. Intravenous secretin in a dose of 5.6 pmol/kg/hr significantly inhibited the gastric acid output stimulated by intravenous pentagastrin in a dose of 160 pmol/kg/hr, from 11.25±1.5 to 5.99±1.34 meq/hr, while lower dose of intravenous secretin (2.8 pmol/kg/hr) failed to inhibit the gastric acid output stimulated by the same dose of pentagastrin. However, the lower dose of intravenous secretin (2.8 pmol/kg/hr) inhibited the gastric acid output significantly from 8.78±1.21 to 6.37±1.62 meq/hr when gastric secretion was stimulated by the lower dose of pentagastrin (80 pmol/kg/hr). The plasma concentrations of secretin during intravenous secretin in a dose of 2.8 pmol/kg/hr was similar to postprandial plasma concentrations of secretin as previously reported. Doubling the dose of intravenous secretin resulted in almost twofold higher plasma concentrations than postprandial plasma concentrations. In addition, the low dose of secretin (2.8 pmol/kg/hr) suppressed the integrated postprandial gastrin response from 13.9±3.7 to 11.2±2.8 ng/min/ml (P=0.05) when endogenous release of secretin was blocked by intravenous cimetidine. Since the dose of pentagastrin and secretin employed in this study fell in a physiologic range, the inhibitory effect of secretin on stimulated gastric acid secretion appears to be a physiologic action in humans. Contrary to the findings in dogs, the inhibitory action of secretin on gastrin release was not statistically significant but was highly suggestive.     

Effect of Pentagastrin,Secretin, and Cholecystokinin on Gastric Secretion of Pepsin in Man

In eight volunteers the effect of pentagastrin (0.15, 1.0 and 6.0 μg/kg body weight/h), secretin (0.5 and 1.0 clinical units/kg b.w./h), and cholecystokinin (CCK) (0.5 and 1.0 Ivy dog units/kg b.w./h) on the gastric secretion of pepsin was investigated to ascertain whether interaction occurred. A high intraindividual variation was found, and also a significant washout of pepsin in the initial period after stimulation. Pepsin secretion was stimulated after pentagastrin (50% above basal level) and even more after secretin (75%-200% above basal level), whereas no stimulation but a tendency for depression was seen after CCK. With the doses of gastrointestinal hormones used in this investigation, no interaction between secretin and CCK on gastric secretion of pepsin in man was demonstrated.     

Cholinergic Effect on the Canine Pancreatic Response to Acidification of the Duodenum

On acidification of the duodenum in 3 conscious dogs with duodenal Thomas fistulas and gastrostomies no change in pancreatic secretion was observed after vagotomy. Cholinergic stimulation significantly increased the pancreatic secretion of fluid and bicarbonate in response to hydrochloric acid in the duodenum. The ratio between the pancreatic secretion of bicarbonate and the amount of acid introduced into the duodenum to elicit that response was 1: 3.2. Urecholine stimulation increased the ratio to 1: 1.7.     

5-羟色胺对大鼠膈下迷走神经传入放电的影响及机制

目的 探讨大鼠外周静脉注射5-羟色胺以及促胰液素(secretin, SEC)对膈下迷走神经传入冲动的影响, 以及5-羟色胺对膈下迷走神经传入冲动影响的机制.方法 采用电生理学方法记录膈下迷走神经传入自发放电为观察指标,观察外周静脉注射不同剂量的5-HT(3、10、30 μg/kg)、5-HT3受体的拮抗剂格拉司琼(1 mg/kg)以及5-HT SEC对其的影响.结果 5-HT对膈下迷走神经传入自发放电具有兴奋作用,给予5-HT3受体拮抗剂后神经放电的效应被抑制,大剂量5-羟色胺 促胰液素可增强由单独的大剂量5-HT所致的迷走神经传入放电的兴奋作用.结论 5-HT可能是作用于与迷走传入相关的5-HT3受体兴奋了膈下迷走传入神经自发放电;促胰液素可以增强5-HT对迷走神经传入自发放电的兴奋作用.     

THE ELECTROLYTE AND PROTEIN CONTENTS AND OUTPUTS IN DUODENAL JUICE AFTER PANCREOZYMIN AND SECRETIN STIMULATION IN NORMAL CHILDREN AND IN PATIENTS ITH CYSTIC FIBROSIS.1

The total pancreatic outputs and the secretion rates of fluid volume, protein, bicarbonate, sodium, potassium, calcium and magnesium were studied after pancreozymin and secretin stimulation in 12 control children and in 5 patients with cystic fibrosis of the pancreas (CF). Duodenal contents were collected through a double-balloon, triple-lumen rubber tube, thus avoiding contamination by gastric juce and distal losses. In CF patients, compared to the normal controls, decreased outputs of fluid volume, protein and electrolytes were found. Secretion rates, calculated per kg body weight and per min of fluid volume protein and electrolytes were analyzed separately for the post-pancreozymin and the post-secretin periods. In control children the secretion rates of sodium aad bicarbonate were higher after secretin stimulation, whereas those of protein, calcium, and magnesium were higher after pancreozymin stimulation; secretion rates of fluid volume and potassium did not show any significant difference. In CF patients the secretion rates of sodium, potassium and magnesium were more reduced after secretin whereas those of calcium and protein are more reduced after pancreozymin; the secretion rates of fluid volume and bicarbonate are similarly reduced after both hormonal stimulation. The possible role of a disturbance of the tubular and the acinar secretion of the pancreas in the pathogenesis of cystic fibrosis is discussed.