缩胆囊素、胃泌素及丙谷胺对大鼠胆汁分泌的影响

本文旨在研究五肽胃泌素(P-Gas)、缩胆囊素(CCK)与其受体拮抗剂丙谷胺(PGM)单独静脉输注或联合应用对大鼠胆汁流量及胆汁成分排泌量的影响。结果表明:(1)P-Gas无利胆作用;(2)CCK-8仅少量增加胆汁及 HCO_3~-的分泌量;(3)PGM 明显地增加胆汁及胆汁中 HCO_3~-和 CI~-的排泌量,但胆酸分泌量不增加;(4)当 CCK-8 2.3μg/(kg·h)静脉灌注与 PGM 200mg 灌胃联合应用时,胆汁、HCO_3~-和 CI~-的排泌量进一步增加,但P-Gas 2μg/(kg·h)与 PGM 联合应用时的胆汁排泌量低于单独应用 PGM 组。以上结果证明:PGM 有明显的促胆汁分泌作用,其机制属于非胆酸依赖性利胆、而CCK-8只是胆汁分泌的微弱刺激剂,P-Gas 则无利胆作用。在 CCK-8与 PGM 二组间,似有促胆汁分泌的协同作用;但表现在 P-Gas 与 PGM 二组间的作用,似为一种拮抗作用。     

刺激迷走神经和酸化十二指肠对狗胰液分泌的相互影响

用5条制备有 Thomas 胰瘘和胃瘘的狗作慢性麻醉实验,观察刺激迷走神经和酸化十二指肠对胰液分泌的相互影响,结果如下:1.在酸化肠的情况下,刺激迷走神经所引起的胰蛋白质和碳酸氢盐的排出量显著增多,其效应超过单独刺激迷走神经和酸化肠所产生效应之和。2.在酸化肠引起胰分泌停止后的短时间内,再刺激迷走神经,胰液分泌的潜伏期缩短,蛋白质和碳酸氢盐排出量增多。3.阻断迷走冲动或注射阿托品后,酸化肠所引起胰液的分泌明显减少。4.用利多卡因麻痹肠粘膜后,酸化肠所引起胰液的分泌也明显降低。这些结果提示,在酸化十二指肠引起胰液分泌的机制中,有迷走神经和局部神经参与,迷走冲动和促胰液素及促胰酶素共同作用靶器官时,有相互加强作用,一旦迷走冲动被阻断,这两种激素的作用即明显降低。     

促胰液素、八肽胆囊收缩素和迷走神经刺激对狗胰液和血清中胰多肽含量的影响

对10只麻醉下主胰管内插置导管的家狗进行急性实验。用放射免疫测定法测定静脉注射促胰液素(8μg/kg)和八肽胆囊收缩素(CCK_8,40ng/kg)以及电刺激胸迷走神经前后的胰液和血清中胰多肽的含量。结果表明,基础胰液中含有大量胰多肽免疫活性物质,平均排出量为3130±2200pg/15min,其平均浓度高于血清水平40倍左右,但是个体之间的变异范围较大。当静脉注射促胰液素和 CCK_8以及电刺激胸迷走神经后,胰液胰多肽排出量和血清胰多肽水平均增多,其中以电刺激迷走神经后尤为明显。高峰都在刺激后15min 内出现。经促胰液素,CCK_8和迷走神经刺激后,胰液中胰多肽排出量比刺激前分别增加105%,52%和200%。外源性促胰液素或 CCK_8刺激后,胰液中胰多肽与 HCO_3~-出量之间或胰液中胰多肽与淀粉酶排出量之间,分别均呈一致的关系。本文结果提示,胰多肽不仅是一种内分泌,它亦具有外分泌的特性。迷走神经、促胰液素和胆囊收缩素对胰多肽的释放具有调节作用。     

五肽胃泌素和胆囊收缩素对血管灌流大鼠离体胃运动的影响

用血管灌流大鼠离体胃制备,研究五肽胃泌素(G5)和八肽胆囊收缩素(CCK8)对胃窦收缩运动的影响。结果表明:(1)血管灌流G5和CCK8都能显著兴奋胃窦收缩运动,并有量效关系;(2)抗胃泌素血清(1:100)可完全取消G5对胃窦收缩运动的兴奋作用;(3)CCK受体阻断剂双丁酰环磷鸟苷和抗CCK8血清(1:100)都能完全取消CCK8对胃窦收缩运动的兴奋作用;(4)M受体阻断剂阿托品能完全阻断G5对胃窦收缩运动的兴奋作用,部分阻断CCK8对胃窦收缩运动的兴奋作用。上述结果提示:(1)G5可特异性兴奋血管灌流大鼠胃窦收缩运动,该作用通过壁内胆碱能神经系统介导;(2)CCK8对血管灌流大鼠胃窦收缩运动亦有特异性兴奋作用,该作用只是部分与壁内胆碱能神经系统有关。     

促胰液素和生长抑素经血管灌流大鼠离体胃抑制胃酸分泌

本工作利用血管灌流离体大鼠胃研究促胰液素和生长抑素对泌酸的影响及其与内源性前列腺素E(PGE)和前列环素(PGI_2)释放的关系。结果表明:(1)促胰液素和生长抑素都能有效地抑制五肽胃泌素(G_5)促进胃酸分泌的作用,消炎病可翻转这种抑制作用。(2)促胰液素能显著促进PGE和PGI_2代谢产物6-酮-前列腺素F_(1α)(6-Keto-PGF_(1α))释放;生长抑素只能促进FGE释放。消炎痛分别阻断促胰液素对PGE和6-keto-PGF_(1α)释放及生长抑素对PGE释放的促进作用。上述结果提示:(1)促胰液素的抑酸效应由促进PGI_2和PGE释放介导;(2)生长抑素的抑酸效应通过促进PGE释放介导。     

食欲素1受体与胆囊收缩素2受体在细胞内的相互作用分析北大核心CSCD

食欲素1受体(orexin 1 receptor,OX1R)与胆囊收缩素2受体(cholecystokinin receptor,CCK2R)在结肠癌细胞中高表达,且异常表达的OX1R、CCK2R与其配体诱导的结肠癌细胞增殖密切相关,但具体机制尚不清楚。以前的研究证实,OX1R与CCK1R在HT-29细胞中能以二聚体的形式发挥作用。本文利用多种(荧光)共振能量转移技术(FRET)结合免疫共沉淀(Co-IP),进一步研究活细胞中OX1R与CCK2R是否发生相互作用。生物发光能量共振转移(BRET)结果显示,在控制供体(OX1R-Rluc)量不变,而逐渐增加受体(CCK2R-e YFP)转染量时,与无刺激的(对照)细胞比较,食欲素或胃泌素刺激HEK293T细胞5 min,BRET信号伴随受体表达量的增加而增加,并达到最大值。采用荧光共振能量转移技术在HEK293T细胞中,能够检测到OX1R-e YFP与CCK2Re CFP明显的FRET信号。同时,受体漂白FRET(ap FRET)结果揭示,在同时表达OX1R-e YFP和CCK2R-e CFP的细胞膜特定区域,进行受体蛋白(OX1R-e YFP)完全光漂白、破坏了受体-供体之间的相互作用和能量传递后,由于供体(CCK2R-e CFP)荧光强度比漂白前明显增强,其荧光共振能量转移效率(FREPe)明显增加,是对照转染细胞的3.7倍(P<0.05)。此外,基因转染结合Co-IP结果显示,仅有在共转染HA-OX1R与Myc-CCK2R的HEK293T细胞提取液的免疫沉淀物中,可同时检出HA-OX1R、Myc-CCK2R融合蛋白,而在未转染或单转Myc-CCK2R的细胞提取液沉淀物中,却不能同时检出两种融合蛋白。以上结果表明,在活细胞生理条件下,OX1R可与CCK2R相互作用,这为进一步探讨二者相互作用在结肠癌细胞增殖中的作用及相关信号通路提供了新的线索。     

吗啡和内啡素对生殖内分泌活动的影响

内源性鸦片样物质(endogenous opiate like substance)亦称内啡素(endorphins),主要分布在脑、垂体和胃肠道等处。在脑内,内啡素具有选择性的分布。在下丘脑正中隆起区域含量较高,提示它可能对垂体激素的分泌具有重要作用。许多作者报告,给动物脑室注射微量的β-内啡肽或脑啡肽,即可明显地促进垂体前叶促肾上腺皮质激素(ACTH)、生长激素(GH)和促甲状腺激素(TSH)的分泌,同时对垂体促性腺激素的分泌亦有明显的影响。因此内啡素是体内调制生殖内分泌活动的一个重要因素。     

消退素:内源性促炎症消退新介质

消退素是近期通过脂质组学方法从炎症消退期腹腔渗出液中分离出的由ω-3多不饱和脂肪酸衍生的生物活性分子。新近研究发现消退素具有限制中性粒细胞的过度活化和募集、促进巨噬细胞吞噬凋亡中性粒细胞等功效,并在脓毒症、哮喘等炎症动物模型中展示出良好的抗炎促消退效应。因而,消退素成为继脂氧素之后备受关注的内源性促炎症消退新介质。     

禁食和复投喂对大口黑鲈胆囊收缩素及其受体基因表达的影响

为研究大口黑鲈(Micropterus salmoides) 胆囊收缩素(Cholecystokinin, CCK)和其受体(Cholecystokinin receptor, CCKR)基因在摄食活动中的功能, 研究通过克隆得到CCK1、CCK2、CCK1R和CCK2R基因的编码区序列, 其长度分别为414、387、1368和1359 bp, 分别编码137、128、455和452个氨基酸。荧光定量结果表明CCK1和CCK2基因均在脑组织中高表达, 其次为肠道组织, 而CCK1R和CCK2R基因分别在胆囊和脑组织中高表达。在摄食后24h内, CCK1、CCK2、CCK1R和CCK2R基因的相对表达量呈先升高后下降趋势, 其中CCK1、CCK1R和CCK2R基因在摄食后3h相对表达量达到最高值, 而CCK2基因在摄食后12h相对表达量达到最高值(P<0.05)。禁食过程中CCK1、CCK1R和CCK2R基因相对表达量在禁食14d时显著升高(P<0.05)。复投喂后CCK1、CCK1R和CCK2R基因的相对表达趋势与餐后表达趋势相似, 呈先升高后降低趋势。但在禁食和复投喂过程中CCK2基因相对表达量并无显著变化。综上所述, 研究结果推测CCK1基因可能与CCK1R、CCK2R基因结合, 作为饱腹信号因子, 通过抑制食欲调控大口黑鲈摄食、消化等生理过程; 而CCK2基因可能作为短期食欲因子调节摄食活动。研究结果可为大口黑鲈摄食活动调节提供理论依据。     

酸化十二指肠引起胆囊收缩的机制探讨

本工作采用制备有 Jones 胆囊插管、Thomas 胰瘘和胃瘘的狗,以胆囊压为指标,探讨盐酸注入十二指肠引起胆囊收缩的机制。结果如下:(1)盐液注入十二指肠使胆囊压升高后,静脉注射阿托品、六烃季铵和苯海拉明可使胆囊压下降;注射酚妥拉明、心得安和纳洛酮无效。上述各种受体阻断剂均不影响八肽胆囊收缩素(CCK8)的作用。(2)普鲁卡因阻断颈迷走神经,可抑制盐酸的效应;阻断解除后,盐酸效应可完全恢复;而阻断或切断颈迷走神经均不影响 CCK8的作用。(3)预先注射新斯的明可易化阈下浓度盐酸的效应,但不影响阐下和阈上剂量 CCK8的作用。(4)肠道灌流利多卡因-盐酸溶液可抑制盐酸的效应,而灌流阿托品-盐酸溶液则先加强而后抑制盐酸的效应。上述结果提示,盐酸引起的胆囊收缩,除体液因素 CCK 外,尚有胆碱能神经因素参与,其感受器在肠粘膜,其作用环节在肠道,可能对盐酸引起的 CCK 释放起易化作用。此外,还和组织胺释放有关。     

The influence of cholecystokinin, vasoactive intestinal peptide and secretin on pancreatic and biliary secretion in laying hens

White Leghorn hens, 14-29 weeks old, were surgically fitted with cannulas for collecting pancreatic and biliary secretions, and a jugular cannula for continuous infusion of either cholecystokinin (CCK), vasoactive intestinal peptide (VIP), or secretin. As compared to secretory levels during saline infusion, CCK significantly stimulated biliary flow and biliverdin concentration in bile; VIP significantly depressed biliverdin concentration but enhanced bicarbonate secretion in both pancreatic and biliary secretions, and also increased total pancreatic flow. Secretin depressed biliary flow and increased pancreatic bicarbonate release. The principal hormonal regulator of biliary secretion appears to be CCK, and that of pancreatic secretion to be VIP.     

Effect of acute hyperglycemia on basal, secretin and secretin + cholecystokinin stimulated exocrine pancreatic secretion in humans

Pancreatico-biliary secretion is reduced during acute hyperglycemia. We investigated whether alterations in pancreatico-biliary flow or volume output are responsible for the observed reduction in duodenal output of pancreatic enzymes and bilirubin during hyperglycemia. Eight healthy subjects were studied on two occasions during normoglycemia and hyperglycemia (15 mmol/l). Pancreatico-biliary output was measured by aspiration using a recovery marker under basal conditions (60 min), during secretin infusion (0.1 CU/kg.h) for 60 min and during secretin + CCK (0.5 IDU/kg.h) infusion for 60 min. Secretin was infused to stimulate pancreatico-biliary flow and volume output. Secretin significantly (P<0.005-P<0.05) increased volume and bicarbonate output and CCK significantly (P<0.01) increased the output of bilirubin, pancreatic enzymes, bicarbonate and volume, both during normoglycemia and hyperglycemia. During hyperglycemia basal, secretin stimulated and secretin + CCK stimulated total pancreatico-biliary output were significantly (P<0.005-P<0.05) reduced compared to normoglycemia. The incremental outputs, however, were not significantly different between hyper- and normoglycemia. Pancreatic volume output was significantly (P<0.05) reduced during hyperglycemia compared to normoglycemia under basal conditions (31+/-16 m/h versus 132+/-33 m/h) during secretin infusion (130+/-17 ml/h versus 200+/-34 m/h) and during secretin + CCK infusion (370+/-39 ml/h versus 573+/-82 ml/h). Plasma PP levels were significantly (P<0.05) reduced during hyperglycemia. It is concluded that 1) hyperglycemia significantly reduces basal pancreatico-biliary output 2) the incremental pancreaticobiliary output in response to secretin or secretin + CCK infusion is not significantly affected during hyperglycemia, 3) a reduction in volume output contributes to the inhibitory effect of hyperglycemia on pancreatico-biliary secretion, 4) hyperglycemia reduces PP secretion suggesting vagal-cholinergic inhibition of pancreatico-biliary secretion and volume during hyperglycemia.     

Effects of pancreatic polypeptide on biliary flow and bile acid secretion stimulated by secretin and cholecystokinin in the conscious pig

Fourteen castrated male Large White pigs, weighing 42.5 +/- 1.0 kg, were fitted with biliary and duodenal fistulae for biliary secretion studies. Furthermore, catheters were placed in a carotid artery for blood sampling and in a jugular vein for peptide infusion. Bile was automatically restituted to the animals and continuously sampled for analysis on experimental days. Following an 8 day recovery period, infusion studies were performed after an overnight fast. After a 30 min basal period, sustained biliary flow and bile acid output were obtained and maintained throughout the assay with secretin (36 pmol/kg/h) and CCK-8 (600 pmol/kg/h) infusion. Then, 200, 400, 600, 800 or 1200 pmol/kg/h of porcine pancreatic polypeptide (PP) were infused for 60 min. Secretin plus CCK infusion was continued for 1 h after PP infusion was stopped. Each dose of PP was given on a separate day. Biliary flow was not affected by PP except for the dose of 400 pmol/kg/h. On the contrary, bile acid concentration and output decreased with the lowest dose of PP (200 pmol/kg/h). As soon as the first dose of PP was infused, bile acid concentration and output fell to about 60% of values obtained with secretin plus CCK. Plasma levels of PP were below or similar to postprandial values for 200, 400 and 600 pmol/kg/h and they were significantly larger with 800 and 1200 pmol/kg/h. Bile acid concentration and output did not return to values obtained with secretin plus CCK infusion after cessation of PP infusion. In conclusion, porcine PP given in physiological doses to the pig decreases bile acid output whereas biliary flow remains unaffected.     

Biliary excretion of inorganic electrolytes: its role in hepatic bile formation

To define the role of inorganic electrolyte secretion in hepatic bile formation, the effects of secretin, glucagon, and differently structured bile acids on bile flow and composition were studied in the dog, guinea pig, and rat. In the dog and guinea pig, secretin (2.5-10 clinical units X kg-1 X 30 min-1) increased bile flow and bicarbonate concentration in bile, a finding consistent with the hypothesis that the hormone stimulates a bicarbonate-dependent secretion possibly at the level of the bile ductule-duct. In the rat, secretin (5-15 CU X kg-1 X 30 min-1) failed to increase bile secretion. Glucagon (1.25-300 micrograms X kg-1 X 30 min-1) increased bile flow in all the three species, and produced no changes in biliary bicarbonate concentrations in the dog and rat. In the guinea pig, however, glucagon choleresis was associated with an increase in bicarbonate concentration in bile, similar to that observed with secretin. The choleretic activities of various bile acids (taurocholate, chenodeoxycholate, glycochenodeoxycholate, tauroursodeoxycholate, and ursodeoxycholic acid, infused at 30-360 mumol X kg-1 X 30 min-1) were similar in the rat (6.9-7.2 microL/mumol), but different in the guinea pig (11-31 microL/mumol). In the latter species, the more hydrophobic the bile acid, the greater was its choleretic activity. In all instances, bile acid choleresis was associated with a decline in the biliary concentrations of chloride, but with no major change in bicarbonate levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of the neuropeptide,bombesin, in bile secretion.

Since ancient times, bile secretion has been considered vital for maintaining health. One of the main functions of bile secretion is gastric acid neutralization with biliary bicarbonate during a meal or Pavlovian response. Although the liver has many extrinsic and intrinsic nerve innervations, the functional role of these nerves in biliary physiology is poorly understood. To understand the role of neural regulation in bile secretion, our recent studies on the effect of bombesin, a neuropeptide, on bile secretion and its underlying mechanisms will be reviewed. Using isolated perfused rat livers (IPRL) from both normal and 2 week bile duct ligated rats, as well as hepatocyte couplets and isolated bile duct units (IBDU) from normal rat livers, bombesin was shown to stimulate biliary bicarbonate and fluid secretion from bile ducts. Detailed pH studies indicated that bombesin stimulated the activity of Cl-/HCO3- exchanger, which was counterbalanced by a secondary activation of electrogenic Na+/HCO3- symport. Quantitative videomicroscopic studies showed that bombesin-stimulated fluid secretion in IBDU was dependent on Cl- and HCO3- in the media, anion exchanger(s), Cl- and K+ channels, and carbonic anhydrase, but not on the microtubular system. Furthermore, this bombesin response is inhibited by somatostatin but not substance P. Finally, studies of secondary messengers in isolated cholangiocytes and IBDU indicated that bombesin had no effect on intracellular cAMP, cGMP, or Ca++ levels in cholangiocytes. These results provide evidence that neuropeptides such as bombesin can directly stimulate fluid and bicarbonate secretion from cholangiocytes by activating luminal Cl-/HCO3- exchange, but by different mechanisms from those established for secretin. These findings, in turn, suggest that neuropeptides may play an important regulatory role in biliary transport and secretion. Thus, this neuropeptidergic regulation of bile secretion may provide a plausible mechanism for the bicarbonate-rich choleresis seen with meals or Pavlovian response.     

Cyclic nucleotides, calcium, bicarbonate, and protein secretion in canine pancreatic juice in response to cholecystokinin-pancreozymin.

The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin-pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg-1 h-1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg-1 h-1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg-1 h-1 of CCK and later for 12 and 24 U kg-1 h-1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin.     

Regulation of biliary protein secretion in dogs

The biliary secretion of protein in response to bile acids and other agents known to increase bile flow was examined in a chronic bile fistula dog model. Infusion of 25, 50, or 75 mumole/kg/hr sodium taurocholate after 3 hr of bile fistulization increased biliary protein output significantly by 52, 86, and 108% respectively compared to preinfusion values. A proportionate increase in biliary albumin output during taurocholate choleresis was demonstrated. Protein outputs during bile fistulization without taurocholate replacement were unchanged. The non-micelle-forming bile acid dehydrocholate markedly increased bile flow but did not change protein output. Similarly, the hormonal choleretics glucagon and secretin caused significant decreases in biliary protein concentration but no change in protein output. These data indicate a correlation between biliary protein secretion and bile acid-dependent bile flow. It is likely that regulation of certain proteins is dependent on the micelle-forming properties of bile acids.     

Biliary lipid secretion in the rat. The uncoupling of biliary cholesterol and phospholipid secretion from bile acid secretion by sulfated glycolithocholic acid

Glycolithocholic acid and its sulfated derivative are major metabolites of the secondary bile acid lithocholic acid in man. Both compounds are known to induce cholestasis in experimental animals. We compared the effects of these endogenous hepatotoxins on bile production and biliary lipid composition in rats with chronic biliary drainage. The compounds were administered enterally at relatively low rates (5-50% of the rats' endogenous bile acid secretion in these experiments) to simulate enterohepatic circulation. Both compounds were substantially secreted into bile (more than 90% of dose); sulfated glycolithocholic acid unchanged and glycolithocholic acid after hepatic hydroxylation predominantly in the form of glyco-beta-muricholic acid (cf. Kuipers et al. (1986) Am. J. Physiol. 251, G189-G194). Neither glycolithocholic acid nor its sulfated derivative affected the biliary excretion of endogenous bile acids or bile flow in these experiments. In spite of this, phospholipid and cholesterol secretion were significantly reduced by sulfated glycolithocholic acid but were not altered by glycolithocholic acid. Phospholipid and cholesterol secretion rapidly decreased to 25 and 50% of their initial values, respectively, at biliary output rates of sulfated glycolithocholic acid up to 2 mumol/h, and did not further decrease when this output was increased to 6 mumol/h. Small unilamellar liposomes consisting of cholesterol, [Me-14C]choline-labeled phosphatidylcholine, phosphatidylserine and [3H]cholesteryl oleate in a 5:4:1:0.1 molar ratio were employed to label intrahepatic lipid pools. Administration of sulfated glycolithocholic acid slightly reduced bile acid synthesis from [3H]cholesteryl oleate, but significantly reduced the biliary secretion of [14C]phospholipid. Glycolithocholic acid did not affect the hepatic processing of liposomal lipids. It is concluded that sulfated glycolithocholic acid at low doses causes the uncoupling of biliary lipid secretion from that of bile acids, which might represent in initiating event in sulfated glycolithocholic acid hepatotoxicity.     

The secretion of adenosin 3',5'-monophosphate after hydrokinetic and ecbolic stimulation in the canine pancreas (author's transl)

The secretion of cAMP is studied in vivo and in the isolated perfused canine pancreas after administration of secretin and CCK or caerulein in comparison with hydrokinetic or ecbolic secretory events as well as with the magnitude and time course of changes in tissue cAMP. 1) The total output of cAMP and pancreatic juice shows a significant and positive correlation after stimulation with secretin. The linear correspondence between cAMP concentration and secretory rates of pancreatic juice beyond 3 ml/5 min and their non-linear, reciprocal correlation at lower rates of fluid secretion point to an active as well as to a passive secretory mechanism for cAMP. 2) CCK and caerulein increase secretion of cAMP too. The output of cAMP however neither corresponds to the time course of protein secretion nor correlates quantitatively with the latter. 3) The behaviour of cAMP secretion and concentration in the pancreatic juice after administration of secretin and CCK or caerulein as well as differs from the changes in tissue cAMP levels. The respective maximum of cAMP output after addition of secretin or ecbolic secretagogues during the greatest decrease in cellular cAMP levels yields on the average about 1% of the estimated reduction in total tissue cAMP content. The results indicate a functional coherence in secretion of pancreatic juice and cAMP but oppose the assumption, that essential amounts of cAMP are released during exocytosis of zymogen granules. The secretion of cAMP may be possibly influenced by cytoplasmatic cAMP levels, but neither reflects the present changes in cellular cAMP nor seems to be of a regulatory importance for the latter.     

Hepatic bile and pancreatic exocrine secretions evoked by gastrointestinal peptides in sheep

The secretory response of hepatic bile and exocrine pancreas to gastrointestinal peptides has been studied in chronically cannulated sheep. Pancreatic juice flow and protein output were evoked dose dependently by intraportal injection of secretin, CCK-8, caerulein, VIP and neurotensin. However, biliary secretion was evoked by only secretin. Biliary and pancreatic exocrine secretions were enhanced by delivered gastric juice into the duodenum as followed by the increased plasma concentration of immunoreactive secretin (IRS). Results suggest that secretin is the major peptide that regulates pancreatic exocrine secretion and hepatic bile production in the sheep.