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. CCK-stimulated amylase release was dose-dependently inhibited by ghrelin. As shown in Fig. National Library of Medicine They were fasted overnight, with continued access to water, prior to experiments. The rats were anesthetized with a single injection of urethane. official website and that any information you provide is encrypted The results are expressed as means s.e.m. Adeghate E, Ponery AS, Pallot D, Parvez SH, Singh J. Food Funct. The pancreas was perfused with modified Krebs-Henseleit solution (pH 7.4, 305 mosmol/kg water) through the celiac and superior mesenteric arteries at a flow rate of 1.2 ml/min using a minipuls pump (Gilson, France). These amino acids have greater effects on stimulating pancreatic secretion, inhibiting gastric emptying, regulating small bowel motility, and causing Acini were pre-incubated at 37 C with minimal shaking for 60 min, followed by treatment with different agonists in 1 ml aliquots in polystyrene vials for the indicated times. Federal government websites often end in .gov or .mil. The functional unit of the exocrine pancreas is composed of an acinus and its draining ductule (Fig. The present studies demonstrate that ghrelin is a potent inhibitor for stimulated pancreatic protein secretion in vivo. 2000). The combined actions of the pancreatic proteases and pepsin from the stomach result in the formation of oligopeptides and free amino acids. Bethanechol at an infusion rate of 3 mg kg1 h1 stimulated pancreatic protein secretions by 5 0.9-fold at 45 min (n = 6, P < 0.05; Fig. The previous report states that 5-HT3 receptor antagonists significantly increased pancreatic fluid and protein outputs [14]. To investigate effects of intrapancreatic neuronal activation, electrical field stimulation (EFS) was carried out with applying biphasic square waves (parameters: 12 V, 2 ms and 8 Hz for 45 min) to the isolated pancreas through a pair of coiled platinum electrodes immersed in the experimental chamber 5 cm apart [10]. Accessibility 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. 1991; Chey, 1993). Distribution of serotonin and its effect on insulin and glucagon secretion in normal and diabetic pancreatic tissues in rat. To investigate pancreatic digestive enzyme secretion, activity of representative enzyme -amylase was measured. 1989). The human pancreas has a large capacity for synthesizing protein (mostly digestive enzymes). *The value is significantly (p<0.05) different from that of CCK alone. These data suggest that intrapancreatic serotonergic nerves play an inhibitory role in pancreatic exocrine secretion and an important role in the insulin action or release. 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. The .gov means its official. Disclaimer. Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. government site. Identification of cells that express 5-hydroxytryptamine1A receptors in the nervous systems of the bowel and pancreas. In rats, ghrelin has been found to stimulate food intake (Wren et al. In addition to the digestive enzymes, the acinar cell secretes a trypsin inhibitor, pancreatic secretory trypsin inhibitor (PSTI). MeSH This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (KRF-2008-313-E00041). These results indicate that serotonin is involved in regulation of pancreatic secretion. The bicarbonate comes from ductal epithelial cells in the pancreas. Differences were considered significant when P values were less than 0.05. The function of centroacinar is not established but may play a role in providing progenitor cells for pancreatic cell lineages. 1997; Papotti et al. Accessibility Recently, it has been reported that pancreatic exocrine secretion is regulated by the interaction of hormones and the neural system [5]. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). of 6 experiments. Please enable it to take advantage of the complete set of features! 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. National Library of Medicine The results are expressed as means s.e.m. Amylase output was also elevated from 18.254.58 l/15 min to 48.499.51 l/15 min in peak level. 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. In contrast to acinar cells, the ducts secrete a large volume of fluid with a high concentration of bicarbonate. The pancreas has a portal system called the 'insulo-acinar axis' between the endocrine part and the exocrine part. Pancreatic cancer initiates hyperinsulinemia and delays insulin secretion peak, while insulin mediates cancer cell metabolism to maintain PDA survival with proliferation, and insulin also stimulates the formation of a tumor-promoting microenvironment around cancer cells. 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. 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. Biomed Res Int. CCK-induced increases in secretory volume were also inhibited by ghrelin infusion. Isolated perfused rat pancreas model could eliminate effects of all external nerves and other gastrointestinal hormones perfectly. To confirm pancreatic exocrine secretion stimulated by CCK-8 in the isolated perfused rat pancreas, CCK-8 (Squibb, USA) at a concentration of 5 pmol added to the perfusate contained 5.6 mM glucose for 60 minutes. Received 2001 May 18; Accepted 2001 Jul 26. The Pancreas: Biology, Pathobiology, and Dis-ease. WebIn pancreatic lobules of guinea pig and rat, WIN55,212 significantly inhibited amylase release stimulated by KCl depolarization through inhibition of presynaptic acetylcholine release, but did not modify basal, carbachol- or CK-stimulated amylase secretion. Central effect of ghrelin, an endogenous growth hormone secretagogue, on hypothalamic peptide gene expression. Study of Antiobesity Effect through Inhibition of Pancreatic Lipase Activity of Diospyros kaki Fruit and Citrus unshiu Peel. Copyright 2023 McqMate. The acinar cells contained within the pellet were lysed with a sonicator for 15 s. Amylase content in both the pellet and the supernatants was determined using the Phadebas reagent and expressed as a percentage of total cellular amylase content. Mori K, Yoshimoto A, Takaya K, Hosoda K, Ariyasu H, Yahata K, Mukoyama M, Sugawara A, Hosoda H, Kojima M, Kangawa K, Nakao K. Kidney produces a novel acylated peptide, ghrelin. Ghrelin (1.2 and 12 nmol kg1 h1) was infused from 45 to 150 min and CCK-8 (400 pmol kg1 h1) from 60 to 150 min. The site is secure. Infusion pumps and thermal barriers were obtained from Harvard Apparatus, Inc. (South Natic, MA, USA). Even, the only Food and drug administration (FDA) approved antiobesity drug, orlistat, is also an inhibitor of pancreatic lipase. Regulation of exocrine pancreatic secretion during the intestinal phase of digestion. Epub 2016 Jul 27. False. An official website of the United States government. Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini. Moreover, this present study did not measure insulin volume in the perfusate. The interaction of the lysosomal enzyme mannose 6-phosphate with its receptor leads to formation of vesicles that transport this complex to the lysosome, delivering the enzyme. 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. Human amylase is secreted by both the pancreas and salivary glands. Park HS, Kwon HY, Lee YL, Chey WY, Park HJ. Guan XM, Yu H, Palyha OC, McKee KK, Feighner SD, Sirinathsinghji DJ, Smith RG, Van der Ploeg LH, Howard AD. After a 40-minute basal period, a test meal was eaten to stimulate cholecystokinin release and pancreaticobiliary responses. Similar to NPY, ghrelin appears to act on the intrapancreatic neurons to inhibit pancreatic protein secretion. Masuda Y, Tanaka T, Inomata N, Ohnuma N, Tanaka S, Itoh Z, Hosoda H, Kojima M, Kangawa K. Ghrelin stimulates gastric acid secretion and motility in rats. Collagenase was obtained from Boehringer Mannheim (Mannheim, Germany). Lee YL, Kwon HY, Park HS, Lee TH, Park HJ. Spiperone hydrochloride, a serotonin antagonist, significantly enhanced pancreatic secretion of both fluid and amylase. Animals were cared for under pathogen-free guidelines and housed at constant ambient temperature with alternating light-dark cycles of 12 h. They were permitted free access to water and standard rodent laboratory chow. Effect of reserpine on pancreatic exocrine secretion induced by mesencephalic reticular stimulation in rats. WebPancreatic beta cell secretion is inhibited by the increase in sympathetic drive that occurs during exercise? The duct cell is rich in CA. 5, these values of pancreatic volume flow and amylase output under 18 mM glucose background were significantly inhibited by administration of serotonin (p<0.05). These data suggest that action of serotonin on pancreatic exocrine secretion is dependent on insulin. The exocrine pancreas has been of considerable interest to physiologists and other scientists for quite some time; in fact, the first demonstration of a hormone action was in the pancreas around the turn of the 20th century.1 The pancreas has been the major organ used to demonstrate the mechanisms of synthesis and transport for exportable proteins2 as well as the signaling pathways involved in regulated protein secretion.3 This chapter presents a concise description of the current understanding of pancreatic physiology. Michaloudi EC, Papadopoulos GC. Male Sprague-Dawley rats (200250 g) obtained from Harlan (Indianapolis, IN, USA) were used for all experiments. Schonfeld JV, Muller MK, Demirtas B, Soukup J, Runzi M, Goebell H. Effect of neural blockade on somatostatin-induced inhibition of exocrine pancreatic secretion. Mulholland MW, Lally K, Taborsky GJ., Jr Inhibition of rat pancreatic exocrine secretion by neuropeptide Y: studies in vivo and in vitro. Epub 2020 Mar 26. In the lysosome the enzyme dissociates from the receptor, which in turn cycles back to the Golgi complex. 2010 (HRF-2010-034). Stimulation of gastric secretion by ghrelin administered by intracerebroventricular injection is mediated by direct central activation of a central vagal mechanism (Date et al. Several recent reports suggest that ghrelin acts within the central nervous system. WebExocrine pancreatic secretions are regulated by hormonal, neural, and paracrine input during the cephalic, gastric, and intestinal phases of secretion. 2000; Wren et al. 2000) or stimulated gastric acid secretion (Masuda et al. Salivary (lingual) and gastric lipases also contribute to fat digestion but in a minor fashion (see Chapter 49). Li X, Yamada H, Morita S, Yamashita Y, Kim Y, Kometani T, Narang N, Furuta T, Kim M. Nutrients. WebThe endocrine function is performed by islets that are embedded within the exocrine pancreatic tissue and secrete hormones such as insulin, glucagon, somatostatin, and Similarly, spiperone hydrochloride-induced pancreatic exocrine secretion was partially inhibited by atropine in this study. Gastrointestinal Teaching Project, American Gastroenterological Association, 2003.). 2000). Hormonal control of pancreatic exocrine secretion. Antiobesity therapeutics; Orlistat; Pancreatic lipase enzyme; Pancreatic lipase inhibitors; Triacylglycerides. Acini were purified by centrifugation at 50 g for 3 min in KRB solution containing 4 % BSA, and resuspended in incubation buffer that consisted of Hepes buffered Ringer (HRB) solution containing (mm): 127 NaCl, 1.28 CaCl2, 0.55 MgCl2, 4.7 KCl, 0.55 Na2HPO4, 10 Hepes, 11 glucose, 2 glutamine, 1 % (v/v) Eagle's minimal essential amino acids, 0.1 mg ml1 soybean trypsin inhibitor and 10 mg ml1 BSA, oxygenated with 100 % O2, and adjusted to pH 7.4. 2020 Apr;12(8):741-757. doi: 10.4155/fmc-2019-0284. Corresponding to: Yun-Lyul Lee, Department of Physiology, College of Medicine, Hallym University, 39, Hallymdaehak-gil, Chuncheon 200-702, Korea. FOIA 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. Would you like email updates of new search results? Of note, the alkaline secretions from the pancreas, the biliary system, and the duodenal mucosa neutralize the acid secretion delivered to the duodenum from the stomach. Within the microvilli and in the cytoplasm underlying the apical plasma membrane is a filamentous actin meshwork that is involved in exocytosis of the contents of the zymogen granules.5,6 Secretion is into the lumen of the acinus. Recent studies have supported the hypothesis that this negative feedback control of pancreatic secretion is mediated by cholecystokinin (CCK). The latter observation suggests that ghrelin may regulate gastrointestinal function. The pancreas can maintain its exocrine secretion with perfect isolation of external nerves as intrapancreatic nerves continue basal activity [24]. Data were expressed as multiples of basal secretion. The rats were anesthetized with a single injection of urethane. In the present study, EFS-induced pancreatic exocrine secretion in the isolated perfused rat pancreas was inhibited by serotonin, including volume flow and For the acinus, cholecystokinin (CCK), secretin, acetylcholine (Ach), gastrin-releasing peptide (GRP), vasoactive intestinal polypeptide (VIP), and substance P regulate secretion. 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. This report shows another possibility that serotonin can have both an inhibitory and stimulatory effect on insulin release. As seen in the above results and reports, pancreatic exocrine secretion is controled by a complex set of factors. Amylase released was expressed as the percentage of total tissue content. Subdiaphragmatic vagotomy was performed prior to beginning measurements. Copyright 2021 Elsevier Inc. All rights reserved. c. PaO2 = 40 mmHg. 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 the contents by NLM or the National Institutes of Health. throughout their Academic career. Bethesda, MD 20894, Web Policies 2001) and c-fos mRNA expression in dorsomotor nucleus of the vagus (Date et al. Then it reacted in 37 incubator for 10 minutes. CCK infusion was begun at 60 min in both groups. Acinar cells were incubated with varying concentrations of ghrelin (1011107m) in the presence or absence of CCK-8 (1010m). Furthermore, with rising flow rates there are dramatic changes in the concentrations of chloride and bicarbonate in pancreatic juice. WebThis regulation is complex given that numerous intracellular signaling pathways are coupled to inhibition or stimulation of secretory function. As a library, NLM provides access to scientific literature. Pancreatic flow rate was decreased from 6.691.23 l/15 min to 4.020.31 l/15 min in peak level. Nagain-Domaine C, Presset O, Chariot J, Roz C. Effect of sumatriptan on external pancreatic secretion and its interaction with endogenous norepinephrine in the rat. It is secreted from the acinar cell of pancreas and has strong preference for triacylglycerides over cholesterol esters, phospholipids, and galactolipids. On the other hand, it is reported that 5-HT2 and 5-HT3 receptor antagonists inhibited pancreatic exocrine secretion [16]. In both regimen groups, the (Tel) 82-33-248-2583, (Fax) 82-33-248-1640. Future Med Chem. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matrukura S. A role for ghrelin in the central regulation of feeding. Impact of Grape Seed Powder and Black Tea Brew on Lipid Digestion-An In Vitro Co-Digestion Study with Real Foods. To elucidate these problem more clearly, a dose-dependent experiment of serotonin will be carried out. Atropine blocked significantly meal-stimulated pancreatic digestive enzyme secretion, and the response to graded doses of exogenous CCK was significantly inhibited by both atropine and loxiglumide, a CCK1R antagonist, suggesting that pancreatic enzyme secretion is predominantly dependent on a cholinergic tone and that CCK modulates the
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