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The perfusate contained 5.6 mM glucose (Sigma, USA), 0.1% bovine serum albumin (Sigma, USA) and 3% Dextran T-70 (Sigma, USA), and was continuously oxygenated with 95% O2 and 5% CO2. Lifson N, Lassa CV, Dixit PK. (2000) and Wren et al. In common with synthetic growth hormone secretagogues (GHSs), ghrelin causes growth hormone release in humans and rats following either peripheral or central administration, and from primary cultured pituitary cells (Kojima et al. Ghrelin alone produced no significant change in basal amylase release (Fig. WebThe results indicated that pancreatic enzyme secretion in the rat is subject to feedback inhibition from intestinal trypsin and chymotrypsin, and that trypsin inhibitors stimulate 2000) and to increase body weight (Tschop et al. All reagents were bought from Sigma (USA). As illustrated in Figure 56-5, activation of these enzymes takes place in the intestinal lumen, where a brush-border glycoprotein peptidase, enterokinase, activates trypsinogen by removing (by hydrolysis) an N-terminal hexapeptide fragment of the molecule (Val-Asp-Asp-Asp-Asp-Lys).17 The active form, trypsin, then catalyzes the activation of the other inactive proenzymes. 1989). Effects of intrapancreatic neuronal activation on cholecystokinin-induced exocrine secretion of isolated perfused rat pancreas. Infusions of synthetic rat ghrelin (1.2 or 12 nmol kg1 h1) were begun 15 min before CCK-8 administration and continued for the remainder of the experiment. from four separate experiments. CCK at a dose of 400 pmol kg1 h1 significantly increased amylase secretion from the basal of 3.9 0.6 U min1 to the peak rate of 23.3 U min1 (P < 0.05 vs. basal). FOIA 2000a). CCK-8 was purchased from Research Plus, Inc. (Bayonne, NJ, USA). The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Further study is necessary to study a insulin release for serotonin action mechanism. Pancreatic flow rate was decreased from 6.691.23 l/15 min to 4.020.31 l/15 min in peak level. EFS-induced pancreatic exocrine secretion was completely blocked by tetrodotoxin and partially inhibited by atropine [10]. In: Go VLW, editor. In spite of these dual actions of the pancreas, the effect of serotonin on the pancreas has been controversial. VIP causes (true or false): A) (1978). 2001), suggesting a possible role in regulation of feeding behaviour and energy metabolism. 2023 Feb 15;13(2):274. doi: 10.3390/bios13020274. Phospholipase A2 catalyzes the hydrolysis of the fatty acid ester linkage at carbon 2 of phosphatidylcholine.16 This cleavage leads to the formation of free fatty acid and lysophosphatidylcholine. Then it reacted in 37 incubator for 10 minutes. Briefly, rats that had been fasted overnight were killed by CO2 inhalation, and the pancreata were removed and placed in a Petri dish containing fresh Krebs-Ringer buffer (KRB) solution consisting of (mm): 110 NaCl, 0.5 CaCl2, 1.1 MgCl2, 4.7 KCl, 0.55 Na2HPO4, 32.5 NaHCO3, 22 glucose, 2 glutamine, 0.1 mg ml1 soybean trypsin inhibitor and 1 % (v/v) Eagle's minimal essential amino acids, equilibrated with 5 % CO2-95 % O2, adjusted to pH 7.4. In addition, other types of serotonergic antagonist will be administered to the pancreas to clarify detailed serotonin action on pancreatic exocrine secretion. Careers, Unable to load your collection due to an error. 0.58 mm, O.D. Gastric transit of the enzymes, with appearance of near-normal amounts in the duodenal contents, occurred only after inhibition of gastric secretion and buffering of On the other hand, it is reported that 5-HT2 and 5-HT3 receptor antagonists inhibited pancreatic exocrine secretion [16]. The pancreas was placed in temperature-controlled experimental chamber at 37, which was also continuously supplied with Krebs-Henseleit solution at a flow rate of 0.35 ml/min and oxygenated. Pancreatic juice was collected in polyethylene tube which has volume of 2.4 l/cm then measured length to determine volume flow. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR. Computational approaches for the discovery of natural pancreatic lipase inhibitors as antiobesity agents. There are both peptidergic nerves and cholinergic nerves in the intrapancreatic nerve system [11]. gastrin inhibits histamine secretion from gastric mucosal enterochromaffin-like cells B. histamine stimulates parietal cell acid secretion via an endocrine mechanism C. Through a small incision, a polyethylene cannula (PE10) was advanced into the bile-pancreatic common duct and was secured in place with fine silk suture. Abstract Human pancreatic lipase (triacylglycerol acyl hydrolase EC3.1.1.3) is the most widely studied member of the human lipase superfamily related to carboxyl The final product, glucose, is transported across the intestinal absorptive epithelial cell by a Na+-coupled transport (see Chapter 100).21,22. Newly synthesized proteins can undergo modifications in the endoplasmic reticulum, including disulfide bridge formation, phosphorylation, sulfation, and glycosylation. Presurgical Functional MappingAndrew C. Papanicolaou, Roozbeh Rezaie, Shalini Narayana, Marina Kilintari, Asim F. Choudhri, Frederick A. Boop, and James W. Wheless, the Child With SeizureDon K. Mathew and Lawrence D. Morton, Hematology, Oncology and Palliative Medicine, The functional unit of the exocrine pancreas is composed of an acinus and its draining ductule (, Regulation of exocrine pancreatic secretion during the intestinal phase of digestion. Amylase output of EFS plus atropine was also elevated from 8.081.78 l/15 min to 23.668.37 l/15 min in peak level. Thus, the specific pattern of protease actions leads to physiologic regulation of several organs in the gastrointestinal tract. Volume was recorded and aliquots assayed for protein content. Gastrointestinal Teaching Project, American Gastroenterological Association, 2003. Neural regulation of pancreatic exocrine func-tion. the contents by NLM or the National Institutes of Health. The combined actions of the pancreatic proteases and pepsin from the stomach result in the formation of oligopeptides and free amino acids. Mechanism of action of insulin on pancreatic exocrine secretion in perfused rat pancreas. The bicarbonate comes from ductal epithelial cells in the pancreas. This present study shows that pancreatic exocrine secretion in the isolated perfused rat pancreas had no significant difference between CCK alone administration and CCK plus serotonin administration when perfused with glucose at a dose of 5.6 mM. Supplemental doses were used every 2 h as needed to maintain adequate anaesthesia. Figure 56-2. 2000; Wren et al. Lee YL, Kwon HY, Park HS, Lee TH, Park HJ. Study of Antiobesity Effect through Inhibition of Pancreatic Lipase Activity of Diospyros kaki Fruit and Citrus unshiu Peel. cyclic AMP; glucagon; pancreatic islets; insulin; somatostatin GLUCAGON PLAYS A CRITICAL ROLE inbloodglucosehomeostasis,and its secretion from pancreatic islet -cells is inhibited with rising glucose. Collagenase was obtained from Boehringer Mannheim (Mannheim, Germany). 4, ,55). The higher chloride concentration in the lumen is coupled to a Cl-HCO3 antiport, resulting in an exchange of Cl for HCO3 in the lumen. Peschke E, Peschke D, Hammer T, Csernus V. Influence of melatonin and serotonin on glucose-stimulated insulin release from perifused rat pancreatic islets in vitro. Figure 56-1. glucagon plays a critical role in blood glucose homeostasis, and its secretion from pancreatic islet -cells is inhibited with rising glucose. This complex then attaches to the outer surface of the endoplasmic reticulum, and the signal sequence targets the protein being synthesized into the lumen of the RER. 2000a). Schonfeld JV, Muller MK, Demirtas B, Soukup J, Runzi M, Goebell H. Effect of neural blockade on somatostatin-induced inhibition of exocrine pancreatic secretion. True. 2000). To test for a direct inhibitory effect of ghrelin on pancreatic exocrine function, dispersed acinar cells were incubated with various doses of the peptide in vitro. Bethanechol was dissolved in saline and administered as a continuous intravenous infusion beginning at the end of the basal collection period. Chey WY. Before 1). However, they differ in molecular weight, carbohydrate content, and electrophoretic mobility.20 Salivary amylase initiates digestion in the mouth and may account for a significant portion of starch and glycogen digestion because it is transported with the meal into the stomach and small intestine, where it continues to have activity. 2020 Oct 21;11(10):8527-8536. doi: 10.1039/d0fo01262a. Our acute and long-term experiments on rats show that pancreatic secretion is significantly inhibited by PPIs. 1999) and localized to gastric oxyntic glands (Date et al. CCK infusion was begun at 60 min in both groups. 56-3). 2001). Other enzymes, such as amylase and lipase, are stored and secreted in their active forms. Hchtebrock HJ, Niebel W, Singer MV, Forssmann WG. 2000). After equilibration period of 30 min, pancreatic juice was collected through the experiment every 15-min. The oligopeptides are further digested by brush-border enzymes (see, Synthesis of digestive enzymes takes place in the internal space of the rough endoplasmic reticulum (RER) (see. Would you like email updates of new search results? Figure 56-3. When there is an increased demand on the RER for protein synthesis or when there is a cell stress that causes unfolding of proteins, the RER responds by increasing synthesis of chaperones and foldases, ceases synthesis of the proteins, and even degrades unfolded proteins using the mechanisms of the unfolded protein response (UPR).28 By keeping proteins in their appropriate conformation, the UPR maintains normal transport of proteins between compartments of the cell. Free amino acids and oligopeptides are transported across the intestinal mucosa by a group of Na+ and H+-coupled transporters.25 It is interesting that only certain amino acids (mostly essential amino acids) can be measured in the lumen during digestion, indicating that the combined action of the proteases is not random and that the products result from the combined specificities of the individual proteases. 2023 Apr 3;15(7):1748. doi: 10.3390/nu15071748. PE10 and PE50 polyethylene tubing was purchased from Becton Dickinson (Sparks, MD, USA). This pH-neutral environment is important for optimal digestive enzyme and intestinal mucosal function. Scheele GA, Palade GE. Another intercellular connection between acinar cells is the gap junction. The abdominal wound was covered with a saline-moist gauze and the rats were maintained at 37 C with a thermal barrier. Human pancreatic lipase (triacylglycerol acyl hydrolase EC3.1.1.3) is the most widely studied member of the human lipase superfamily related to carboxyl esterase. Ghrelin at 12 nmol kg1 h1 abolished 2-DG-stimulated pancreatic secretion. It has been demonstrated to inhibit CCK-stimulated release of amylase and by inhibiting the stimulatory effect of insulin on amylase secretion ( Louie et al ., 1985 ). In rats administered 1.2 and 12 nmol kg1 h1 ghrelin, secretion volume remained unchanged after CCK infusion, averaging 0.35 0.03 and 0.34 0.01 ml per 15 min, respectively. 2000a), the hypothalamic arcuate nucleus (Kojima et al. Nitex nylon mesh (150 m) was obtained from Tetko, Inc. (Kansas City, MO, USA). With the addition of serotonin, pancreatic volume flow and amylase output were significantly inhibited electrical field stimulation (EFS). Secretion of pancreatic bicarbonate and other electrolytes. The Pancreas: Biology Pathobiology and Disease. sharing sensitive information, make sure youre on a federal Biomed Res Int. Secretion of the digestive enzymes occurs by exocytosis. Secretion of pancreatic bicarbonate and other electrolytes. 2010 (HRF-2010-034). The rats were anesthetized with a single injection of urethane. 2, pancreatic flow rate and amylase output were increased. 2000; Nakazato et al. The pancreas has a portal system called the 'insulo-acinar axis' between the endocrine part and the exocrine part. Differences were considered significant when P values were less than 0.05. The acinus (from the Latin term meaning berry in a cluster) can be spherical or tubular, as shown in Figure 56-1, or can have some other irregular form.4 The acinar cells are specialized to synthesize, store, and secrete digestive enzymes. Date Y, Nakazato M, Kojima M, Kuroiwa T, Matsukura S, Kangawa K, Nakazato M. Ghrelin acts in the central nervous system to stimulate gastric acid secretion. These amino acids have greater effects on stimulating pancreatic secretion, inhibiting gastric emptying, regulating small bowel motility, and causing Newer evidence also suggests a HCO3 channel on the apical surface involved in HCO3 secretion and that this HCO3 conductance is likely CFTR.11,12 On the basolateral surface of the duct cell are a Na+,H+ antiport and a Na+,HCO3 cotransport, as well as ATPases (Na+,K+-ATPase, H+-ATPase) and K+ channels. of 6~7 experiments. Ghrelin (12 nmol kg1 h1) was infused from 45 to 150 min and 2-DG (75 mg kg1) was given by intravenous bolus injection at 60 min. 1999). Expression of ghrelin and its related receptor, GHS receptor, in kidney indicates that ghrelin may play an important role in the regulation of renal function (Mori et al. Epub 2006 May 24. This is in agreement with the finding that the neural 5-HT1 receptor was involved in the control of endocrine pancreatic function [17]. The pancreatic duct was also cannulated with Tygon microbore tubing. Exocrine secretions are regulated by endocrine and neurocrine pathways. These enzymes digest starch and glycogen in the diet. Each group contained six animals (two-way ANOVA, P < 0.05). *Departments of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, USA, Departments of Physiology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. Journal of Clinical Endocrinology and Metabolism. Subdiaphragmatic vagotomy was performed prior to beginning measurements. Secretin stimulates secretion by binding to its receptor on the acinar cell and activating adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) in the ductal cell; acetylcholine does so by binding to its receptor and raising intracellular calcium concentrations. H+ is removed from the cell by a basolateral Na+,H+ antiport and a H+-ATPase to maintain a constant intracellular pH. (Signaling mechanisms [second messengers] are shown in Fig. The pancreatic duct cell contains numerous mitochondria for energy generation needed for its ion transport functions. 4). Salivary (lingual) and gastric lipases also contribute to fat digestion but in a minor fashion (see Chapter 49). 2006 Aug;47(8):1852-8. doi: 10.1194/jlr.M600168-JLR200. Buy Membership for Gastroenterology and Hepatology Category to continue reading. B) Secretin stimulates the pancreatic acinar cells to secrete enzymes. Park HS, Kwon HY, Lee YL, Chey WY, Park HJ. Intrinsic pancreatic nerves after mechanical denervation of the extrinsic pancreatic nerves in dogs. As shown in Fig. This figure illustrates ion transport responsible for NaHCO. Exocytosis consists of movement of the secretory granule to the apical surface, the recognition of a plasma membrane site for fusion, and the fission of the granule membrane-plasma membrane site after fusion. The Golgi complex also serves the important function of sorting and targeting newly synthesized proteins into various cell compartments. Fasted rats were killed by CO2 inhalation and pancreata were removed. Another intercellular connection between acinar cells is the gap junction. *The value is significantly (p<0.05) different from that of EFS plus atropine. In combination, these transporters facilitate HCO3 secretion at the apical surface as well as maintain intracellular pH.14 Na+ and water are secreted into the ductal system to counter the electrical and osmotic forces resulting from the HCO3 secretion. The other is Na+,HCO3 cotransport on the basolateral membrane. Apart from the hydrolysis of triacylglycerides, pancreatic lipase may cause the hydrolysis of retinyl esters in vivo. Impact of Grape Seed Powder and Black Tea Brew on Lipid Digestion-An In Vitro Co-Digestion Study with Real Foods. 6). FOIA *The value is significantly (p<0.05) different from that of EFS alone. Newly synthesized proteins can undergo modifications in the endoplasmic reticulum, including disulfide bridge formation, phosphorylation, sulfation, and glycosylation. Brain Research. It is mainly reported that roles of serotonin released from enteric nervous system or enterochromaffin cells in the intestinal mucosa [3]. This 56amino acid peptide inactivates trypsin by forming a relatively stable complex with the enzyme near its catalytic site.18 The function of the inhibitor is to inactivate trypsins that are formed autocatalytically in the pancreas or pancreatic juice, thus preventing disorders such as pancreatitis.19, Human amylase is secreted by both the pancreas and salivary glands. Biochemical and Biophysical Research Communications. Inclusion in an NLM database does not imply endorsement of, or agreement with, Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Wakabayashi I. Each points (, EFS alone; , EFS+5-HT) represent the meanS.E. Epub 2016 Jul 27. 5). National Library of Medicine Corresponding to: Yun-Lyul Lee, Department of Physiology, College of Medicine, Hallym University, 39, Hallymdaehak-gil, Chuncheon 200-702, Korea. In addition to the digestive enzymes, the acinar cell secretes a trypsin inhibitor, pancreatic secretory trypsin inhibitor (PSTI). If these enzymes were active in the pancreas, they would digest the pancreatic gland. While ghrelin inhibited pancreatic protein output in vivo, the effect was indirect because ghrelin did not have an effect when dispersed pancreatic acini were exposed to the peptide in vitro. In the present study, EFS-induced pancreatic exocrine secretion in the isolated perfused rat pancreas was inhibited by serotonin, including volume flow and amylase output. The total daily volume of secretion is 2.5L. The osmolality of pancreatic juice is independent of flow rate. Ion transport by the pancreatic duct cell. Pancreatic flow rate was elevated from 1.290.20 l/15 min in basal to 6.691.23 l/15 min in peak level. Kirchgessner AL, Liu MT, Raymond JR, Gershon MD. 2001) and c-fos mRNA expression in dorsomotor nucleus of the vagus (Date et al. This research was partially supported by Hallym University Research Fund. Other enzymes, such as amylase and lipase, are stored and secreted in their active forms. (Signaling mechanisms [second messengers] are shown in, The acinus (from the Latin term meaning berry in a cluster) can be spherical or tubular, as shown in, Ultrastructure of exocrine cells. Tsujita T, Takaichi H, Takaku T, Aoyama S, Hiraki J. J Lipid Res. Therefore, considering the parallels between Surprisingly, we observed that as long as pancreatic progenitors adhered firmly to any particular ECM-coated TCP plate, NEUROG3-induced endocrine specification was strongly inhibited. 2000; Nakazato et al. The principal inorganic components of exocrine pancreatic secretions are water, sodium, potassium, chloride, and bicarbonate (Fig. The .gov means its official. Similar to NPY, ghrelin appears to act on the intrapancreatic neurons to inhibit pancreatic protein secretion. For the acinus, cholecystokinin (CCK), secretin, acetylcholine (Ach), gastrin-releasing peptide (GRP), vasoactive intestinal polypeptide (VIP), and substance P regulate secretion. WebA. By using the isolated perfused rat pancreas model, all other effects can be eliminated. Figure 56-5. throughout their Academic career. This chapter is devoted to the exocrine pancreas. Each points (, CCK alone; , CCK+ 5-HT) represent the meanS.E. The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology. 4). Trypsinogen and the other proenzymes are then converted to active forms by proteolytic cleavage by trypsin. Infusion pumps and thermal barriers were obtained from Harvard Apparatus, Inc. (South Natic, MA, USA). The median line and the abdominal aorta was carefully dissected and cannulated with PE-50 tubing just above the celiac artery, and then tightly ligated just below the superior mesenteric artery. WebSecretin helps regulate the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate from the ductal cells of the pancreas. This pH-neutral environment is important for optimal digestive enzyme and intestinal mucosal function. WebMethods: Fat hydrolysis was inhibited by intraduodenal perfusion of tetrahydrolipstatin, an irreversible lipase inhibitor. Colipase is believed to form a complex with lipase and bile salts. 1Department of Physiology, College of Nursing, Yanbian University, Yanji 133000, China. The present studies demonstrate that ghrelin is a potent inhibitor for stimulated pancreatic protein secretion in vivo. If these enzymes were active in the pancreas, they would digest the pancreatic gland. The ultrastructure of exocrine cells reflects their specialized function. of 7 experiments. These in vitro studies strongly suggest that the inhibitory actions of ghrelin are not mediated by direct actions on the acinar cells. 2001). Michaloudi EC, Papadopoulos GC. Pancreatic exocrine secretion is regulated by the autonomic nerve system and gastrointestinal hormones. After reaction 2 ml dinitrosalicylic acid solution (1% 3,5 -dinitrosalycylic acid, 30% potassium sodium tartrate, 400 mM NaOH) was put in it and heated in 100 for 5 minutes to appear color of maltose, the reactive product. Bile salts are also important for the full activity of this enzyme. False. Insulin enhanced the action of CCK [19,20] and the interaction of CCK and secretin enhanced pancreatic enzyme secretion mediated by insulin [21]. EFS application, however, pancreatic volume flow and amylase output had no significant change in cholecystokinin (CCK) alone when serotonin was applied under a 5.6 mM glucose background. Hence, the modulation of human pancreatic lipase may represent a new insight in the discovery of a number of therapeutics that can inhibit the absorption of fat in body and can be used in obesity and other related metabolic disorders. What Age Is Considered Elderly? Pancreatic flow rate of EFS plus atropine was from 0.760.09 l/15 min elevated to 2.990.51 l/15 min in peak level. Figure 56-4. The site is secure. Twelve percent 2000b). *P < 0.05 vs. KCl; **P < 0.01 vs. control. Trypsin, chymotrypsin, and elastase are endopeptidases that cleave specific peptide bonds adjacent to specific amino acids. Spiperone hydrochloride, a serotonin antagonist, significantly enhanced pancreatic secretion of both fluid and amylase. Pancreatic flow rate was elevated from 1.250.22 l/15 min to 8.100.98 l/15 in peak level. Central effect of ghrelin, an endogenous growth hormone secretagogue, on hypothalamic peptide gene expression. The observation that PPIs and P-CABs inhibit secretin-evoked Secretion of the digestive enzymes occurs by exocytosis. The https:// ensures that you are connecting to the Infusion of ghrelin at doses of 1.2 and 12 nmol kg1 h1 significantly reduced CCK-stimulated amylase output to 15.6 1.4 U min1 (P < 0.05 vs. CCK alone) and 8.7 U min1 (P < 0.05 vs. CCK alone), respectively. of 6~7 experiments. Epub 2020 Mar 26. In the small The reactive tube was cooling in room temperature for 30 minutes then measured a degree of extinction at 546 nm by spectrophotometer (Kontron, Swiss). The pancreatic duct was also cannulated with Tygon microbore tubing (I.D. Basal pancreatic protein secretion averaged 3.2 0.8 mg h1. Inclusion in an NLM database does not imply endorsement of, or agreement with, Thus, this study was aimed to investigate whether intrapancreatic serotonergic nerves could affect pancreatic exocrine secretion and an action mechanism of the intrapancreatic serotonergic nerves. Stimulation of gastric secretion by ghrelin administered by intracerebroventricular injection is mediated by direct central activation of a central vagal mechanism (Date et al. 2023 Feb 2;14:1097835. doi: 10.3389/fphar.2023.1097835. Tissue homogenates were then assayed for amylase. Carboxylesterase has a broad specificity and will cleave cholesterol esters, lipid-soluble vitamin esters, triglycerides, diglycerides, and monoglycerides. In the stomach, the amylase activity is protected from secreted gastric acid by buffering from the meal and by the protected alkaline environment of salivary and gastric mucus.