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1.
Biologically active peptides in the gastrointestinal lumen 总被引:2,自引:0,他引:2
R K Rao 《Life sciences》1991,48(18):1685-1704
The release of a variety of biologically active peptides into the gastrointestinal lumen via gastric, duodenal and intestinal secretions, as well as in the saliva, pancreatic juice and bile, has been explored. The key features of luminal secretion of peptides such as secretion at high concentrations, neurohormonal regulation, luminal orientation of stimulated secretion, stability of peptides in the gastrointestinal lumen, altered secretion under pathophysiological conditions, and biological activity of luminally administered peptides are discussed. This review develops a detailed picture of the current understanding of luminal secretion of peptides and their possible biological functions under normal and pathophysiological conditions. 相似文献
2.
To explore the mechanisms of gastrin-releasing peptide (GRP)-induced gut functions in man, we investigated the effect on gallbladder contraction, exocrine pancreatic secretion and gastric acid secretion of a recently developed CCK receptor antagonist, loxiglumide, on GRP-stimulated effects in six healthy human subjects. Intravenous infusion of graded doses of synthetic human GRP (1-27 pmol/kg per h) caused significant and dose-dependent increases in pancreatic enzyme and gastric acid secretions and in gallbladder contraction. Intravenous administration of loxiglumide (10 mg/kg per h) abolished GRP-stimulated gallbladder contraction, augmented gastric acid secretion, but did not affect exocrine pancreatic secretion. The results suggest that endogenously released CCK is (1) responsible for GRP-stimulated gallbladder contraction, and (2) involved in regulating gastric acid secretion. The results further suggest that GRP-stimulated pancreatic secretion is not mediated by CCK, but has a direct response of GRP on the exocrine pancreas. 相似文献
3.
I M Jackson 《Federation proceedings》1981,40(11):2545-2552
The hypophysiotrophic hormones isolated from the mammalian hypothalamus are distributed throughout the nervous system of vertebrate species. Although their role in regulating pituitary hormone secretion in mammals is clear, a similar function in lower species has not been established. Thyrotropin-releasing hormone is unable to stimulate thyroid function in amphibia and fish, despite being present in the hypothalamus and brain of these species of high concentration. The tripeptide is also found in high concentration in frog skin, a tissue derived from (or programed by) primitive neuroectoderm that is also a rich source of other peptides structurally related to neural peptides located in mammalian brain and gut. Luteinizing hormone-releasing hormone (LHRH) is able to activate gonadotropin secretion in submammalian species but there is evidence that the LHRH material present in avian, reptilian, and piscine brain is not identical to the mammalian decapeptide. An LHRH-like material present in frog sympathetic ganglia appears to function as a neurotransmitter in this location. Somatostatin is present in high concentrations in the hypothalamus, brain, pancreas, and gastrointestinal tract of all vertebrates and chromatographically is identical to the mammalian material, suggesting that this peptide is an "ancient" molecule with an important role in neuronal pancreatic and digestive function. The hypothalamic releasing hormones are part of a family of neural peptides that have a widespread anatomic and phylogenetic distribution and form a diffuse neuroendocrine system. It an material, suggesting that this peptide is an "ancient" molecule with an important role in neuronal pancreatic and digestive function. The hypothalamic releasing hormones are part of a family of neural peptides that have a widespread anatomic and phylogenetic distribution and form a diffuse neuroendocrine system. It an material, suggesting that this peptide is an "ancient" molecule with an important role in neuronal pancreatic and digestive function. The hypothalamic releasing hormones are part of a family of neural peptides that have a widespread anatomic and phylogenetic distribution and form a diffuse neuroendocrine system. It appears likely that the releasing hormones initially arose with a neurocrine or paracrine function, and that only later in evolution did they acquire the role of regulating adenohypophysial secretion. 相似文献
4.
Clinical applications of somatostatin 总被引:4,自引:0,他引:4
E del Pozo 《Hormone research》1988,29(2-3):89-91
Because of its wide distribution in the organism, natural somatostatin (SRIF) demonstrates an ample spectrum of actions, involving mainly the central neuroendocrine system and the enteropancreatic area. In the former, this peptide may find its field of application in conditions characterized by excessive GH, TSH or ACTH secretion, depending on the central or peripheral cause of the inappropriate hormone control. The inhibitory effect of SRIF on gastrointestinal and pancreatic hormones may be useful in the management of tumors originating in this system and also in the treatment of inflammatory processes such as pancreatitis, in malignant diarrhea, and in gastrointestinal bleeding. A complex action of SRIF and its derivative on insulin release and glucose homeostasis may offer some advantages in the control of unstable diabetes. Dampening of organic functions in the upper digestive tract may also render SRIF and its analogues useful in the exploration of the gallbladder, gastric and pancreatic functions. The effect of such peptides on tissue growth and on the regulation of blood pressure are the subject of present investigations. Cytoprotection, an interesting aspect of SRIF application, is discussed elsewhere in this compendium. Finally, some comments on the possible use of SRIF as an additive to the conventional treatment of burns and sepsis close this review. 相似文献
5.
The effect of intraduodenal sodium bicarbonate, 0.1 M, on exocrine pancreatic secretion and the release of two peptides, secretin and VIP, was studied in anesthetized rats and rabbits, two species largely used in the gastroenterology laboratories. In the rabbit, intraduodenal sodium bicarbonate perfusion had no effect either on exocrine pancreatic secretion or on portal plasma levels of secretin and VIP. By contrast, in the rat, intraduodenal sodium bicarbonate perfusion significantly increased hydroelectrolyte exocrine pancreatic secretion and portal plasma secretin levels. A clear interspecific difference reflecting the different gastrointestinal physiology of both species is observed. 相似文献
6.
E Harada M Niiyama B Syuto 《Comparative biochemistry and physiology. A, Comparative physiology》1986,85(4):729-734
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. 相似文献
7.
Human gastrin-releasing peptide: biological potency in humans. 总被引:3,自引:0,他引:3
P Hildebrand B Werth C Beglinger F Delco J B Jansen C B Lamers K Gyr 《Regulatory peptides》1991,36(3):423-433
Gastrin-releasing peptide (GRP) was infused in graded doses (1-27 pmol/kg per h) to healthy human volunteers to study the effects on gastric, pancreatic and gallbladder functions as well as on gastrin, CCK and PP release. The results were compared to equimolar doses of synthetic bombesin. GRP significantly (P less than 0.05) stimulated gastric and pancreatic secretory responses, gallbladder contraction and gastro-enteropancreatic hormone release in a dose-dependent manner. GRP was found to be equipotent to bombesin with respect to gastric acid secretion, pancreatic enzyme output, gallbladder contraction and plasma hormone release. We conclude (a) that human GRP has similar biologic effects as synthetic bombesin; (b) as GRP is localized exclusively in nerve tissue and has potent effects on different organs, it is a likely candidate for peptidergic control of human gastric, pancreatic and gallbladder functions. 相似文献
8.
The enteric nervous system (ENS: myenteric and submucosal plexuses) of the gastrointestinal tract may have a role in the reduction of food intake by cholecystokinin (CCK). Exogenous cholecystokinin-8 (CCK-8) activates the myenteric plexus and the feeding control areas of the dorsal vagal complex (DVC) of the brainstem. An increasing number of reports, however, have shown that CCK-58 is the sole or the major circulating form of CCK in rat, human and dog, and that it is qualitatively different from CCK-8 in evoking various gastrointestinal physiological responses (e.g., contraction of the gallbladder and exocrine pancreatic secretion). In the current report, we compared the abilities of exogenous CCK-58 to activate the myenteric plexus and the dorsal vagal complex with those of exogenous CCK-8 by quantifying Fos-like immunoreactivity (Fos-LI; a marker for neuronal activation). We report that CCK-58 (1, 3, and 5 nmol/kg) increased Fos-LI in the myenteric plexus (p<0.001) and in the DVC (p<0.001) compared to the saline vehicle. The highest dose of CCK-58 increased Fos-LI more than an equimolar dose of CCK-8 in the myenteric plexus and the area postrema. Thus, CCK-8 and CCK-58 produce the same qualitative pattern of activation of central and peripheral neurons, but do not provoke identical quantitative patterns at higher doses. The different patterns produced by the two peptides at higher doses, in areas open to the circulation (myenteric plexus and area postrema) may reflect endocrine actions not observed at lower doses. 相似文献
9.
A B Leiter A Toder H J Wolfe I L Taylor S Cooperman G Mandel R H Goodman 《The Journal of biological chemistry》1987,262(27):12984-12988
Peptide YY is a 36-residue gastrointestinal hormone which inhibits both pancreatic and gastric secretion. We have isolated a cDNA encoding the peptide YY precursor by screening a rat intestinal lambda gt11 cDNA library with an antiserum directed against the porcine hormone. The nucleotide sequence of the cDNA encodes a 98-residue protein (molecular weight, 11, 121) which has an amino acid sequence identical to that of porcine peptide YY. Rat peptide YY is preceded immediately by a signal sequence and followed by a cleavage-amidation sequence Gly-Lys-Arg plus 31 additional amino acids. Thus the peptide YY precursor is similar in structure to that of two related peptides, pancreatic polypeptide and neuropeptide Y. RNA blot hybridizations reveal that the peptide YY gene is much more actively expressed in pancreas than previously realized. In situ hybridizations localized peptide YY cells exclusively to the exocrine pancreas. The abundance of peptide YY in one of its target organs, the pancreas, suggests a paracrine mechanism for peptide YY in regulating pancreatic enzyme secretion. 相似文献
10.
The glucagon-like immunoreactivity of the gastrointestinal tract is heterogeneous, probably including several different peptides. One of these peptides, glicentine, has recently been extracted and highly purified. Furthermore, by immunocytochemistry a glicentine-like peptide has been reported to occur in the glucagon cell of the pancreatic islets. In the present study we investigated the effects of pure glicentine on insulin release in vivo in mice. The effects were compared with effects of two other peptides, glucagon and GIP. It was found that glicentine had no influence on basal insulin secretion. This was in contrast to equimolar doses of glucagon and GIP, which both stimulated the secretion of insulin. Glucose-induced insulin release was partially inhibited by glicentine. D-glucose, in a dose selected to give a response of 25% of its maximal, raised the plasma insulin concentrations by 44.0 +/- 5.9 microU/ml. The corresponding rise for glicentine plus D-glucose was 22.3 +/- 3.7 microU/ml, i.e. glicentine inhibited glucose-induced insulin released by about 50% (p < 0.01). GIP, on the other hand, enhanced glucose-induced insulin release. This enhancement was diminished by glicentine, a reflection of the inhibition by glicentine of the glucose-induced insulin release. Neither glicentine nor GIP in the doses tested had any effect on insulin secretion induced by cholinergic stimulation. In conclusion, glicentine seems to have no effect on basal insulin release in the mouse, but it partially inhibits glucose-induced insulin secretion. Thus, if the recently demonstrated glicentine-like peptide in the glucagon cell is authentic glicentine, the glucagon cell of the pancreatic islets may contain peptides with stimulatory (glucagon) as well as inhibitory (glicentine) effects on insulin secretion induced by glucose. 相似文献
11.
Norman S. Track 《CMAJ》1980,122(3):287-292
Gastrointestinal endocrinology is the study of the hormonal regulation of digestion. A number of characterized polypeptide hormones have been localized in specific gastroenteropancreatic endocrine cells. The fact that some of these hormones are also found in nerve and brain cells has given rise to the concept of a gut-brain axis. The functional capacities of these endocrine cells are determined by their anatomic location; the luminal exposure of gastroenteric endocrine cells represents an additional avenue for stimulation and release that is not open to pancreatic endocrine cells. Gastroenteropancreatic hormones regulate carbohydrate metabolism, gastric acid secretion, pancreatic exocrine and gallbladder function, gastrointestinal motility and blood flow. These important regulatory hormones may in turn be controlled by a series of gastroduodenal releasing hormones.Diabetes mellitus is the most important metabolic disorder related to a gastroenteropancreatic hormone imbalance. Most tumours producing these hormones are of pancreatic origin and produce a number of hormones; insulinomas and gastrinomas are detected readily because of the serious metabolic distrubances they cause. Other instances of altered circulating concentrations of these hormones result from rather than cause the disease.The challenge of future study is to determine if postprandial changes in the plasma concentrations of these hormones are sufficient or necessary, or both, for the control of digestion. 相似文献
12.
Takenori Onaga Shin Kubagawa Sohtetsu Lee Hitoshi Mineo Seiyu Kato Satoru Naruse Tsuyoshi Ozaki 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1997,167(5):352-360
Temporal coordination between duodenal migrating myoelectric complexes (MMC) and pancreatic exocrine secretion, and the effects
of porcine peptide YY (PYY) on gastroduodenal motility and pancreatic exocrine secretion were examined during the interdigestive
period in conscious mature sheep. Fluid and enzyme secretions from the exocrine pancreas showed a periodic pattern corresponding
to the phases of duodenal MMC, although these secretion rates were maintained at a high level during phase II in sheep. Intravenous
continuous infusion of PYY at doses ranging from 50 to 200 pmol · kg−1 · h−1 or intravenous bolus infusion of PYY at doses ranging from 50 to 200 pmol · kg−1 showed a tendency to prolong the first cycle of the duodenal MMC and significantly shorten the second cycle. However, there
was almost no effect on ruminal contractions from the PYY administration. In the pancreatic exocrine secretion, PYY could
inhibit only bicarbonate secretion at only the highest dose of 200 pmol · kg−1. These results imply that endogenous PYY may play a physiological role in the regulation of the duodenal MMC cycles in sheep
but not in ruminal contractions. PYY seems unlikely to regulate the pancreatic exocrine secretion in normal sheep, because
a supraphysiological dose of PYY was required to inhibit the pancreatic exocrine secretion.
Accepted: 3 March 1997 相似文献
13.
The effect of intravenous gastrointestinal peptide hormone administration on net fluid transport in the small intestine was assessed in the rat. An increased fluid content was observed during vasoactive intestinal peptide, gastric] inhibitory peptide, and neurotensin infusions, and a decreased content with somatostatin, substance P and pancreatic polypeptide, by comparison with the control series. Motilin had no significant effect on luminal fluid volume. These results suggest that several of the gastrointestinal regulatory peptides may have an influence on the processes of fluid absorption and secretion by the small intestine. 相似文献
14.
Rekowski Piotr Borowiec Agnieszka Drużyńska Joanna Kusiak Elżbieta 《International journal of peptide research and therapeutics》1998,5(5-6):417-420
Summary The solid-phase synthesis andin vitro assays on the glucose-induced insulin secretion from rat pancreatic islets of Langerhans with six new chimeric peptides were
performed. All the peptides were built up of the N-terminal galanin (GAL) fragment or its analogues, linked to the C-terminal
portion of substance P (SP) analogues or scyliorhinin I (SCY-I) analogues. Two strong antagonists of the inhibitory effect
of galanin on the glucose-induced insulin release were found: [cycloleucine4]GAL(1–13)-SP(5–11)-amide and GAL(1–13)-[L-norleucine10]SCY-I(3–10)-amide. 相似文献
15.
Recent synthesis of specific, potent bombesin receptor antagonists allows examination of the role of bombesin-like peptides in physiological processes in vivo. We characterized effects of [D-Phe6]bombesin(6-13)-methyl-ester (BME) on pancreatic enzyme secretion stimulated by the C-terminal decapeptide of gastrin releasing peptide (GRP-10), food intake, and diversion of bile-pancreatic juice in rats. In isolated pancreatic acini, BME had no agonistic effects on amylase secretion but competitively inhibited responses to GRP-10, yielding a pA2 value of 8.89 +/- 0.19. In conscious rats with gastric, jugular vein, bile-pancreatic, and duodenal cannulas, basal enzyme secretion (bile-pancreatic juice recirculated) was not affected by the antagonist. Maximal amylase response to GRP-10 (0.5 nmol/kg/h) was inhibited dose dependently by BME, reaching 97% inhibition at a dose of 400 nmol/kg/h. The dose response curve of amylase secretion stimulated by GRP-10 was shifted to the right by 40 nmol/kg/h BME, but maximal amylase response was unaltered, suggesting competitive inhibition in vivo. Liquid food intake and bile-pancreatic juice diversion caused substantial increases in amylase secretion; neither response was altered during administration of 400 pmol/kg/h BME. These results demonstrate that BME is a potent, competitive antagonist of pancreatic responses to bombesin-like peptides in vitro and in vivo. Lack of effect of BME on basal pancreatic secretion or responses to liquid food intake or diversion of bile-pancreatic juice in rats suggests that endogenous bombesin-like peptides do not act either directly or indirectly to mediate these responses. 相似文献
16.
Ana R. Costa Joana Real Célia M. Antunes Júlio Cruz-Morais 《In vitro cellular & developmental biology. Animal》2010,46(1):7-10
It has been postulated that a decrease in Na,K-ATPase-mediated ion gradients may be a contributing mechanism to insulin secretion.
However, the precise role of the Na,K-ATPase in pancreatic β-cell membrane depolarization and insulin secretion signalling
have been difficult to evaluate, mostly because data reporting changes in enzymatic activity have been obtained in cell homogenates
or membrane preparations, lacking intact intracellular signalling pathways. The aim of this work was to develop a method to
characterize Na,K-ATPase activity in intact pancreatic β-cells that will allow the investigation of putative Na,K-ATPase activity
regulation by glucose and its possible role in insulin secretion signalling. This work demonstrates for the first time that
it is possible to determine Na,K-ATPase activity in intact pancreatic β-cells and that this is a suitable method for the study
of the mechanisms involved in the Na,K-ATPase regulation and eventually its relevance for insulin secretion signalling. 相似文献
17.
In this paper we introduce a computer algorithm and programProAnal for analysis of the structure-activity relationshipin a family of evolutionarily related (and/or artificially mutated)proteins/peptides. The program uses aligned amino acid sequenceswith data of their activity (pK, Km, ED50 or any other) andsearches for correlations between data on activity and variousphysico-chemical characteristics of different regions in primarystructures. In automatic mode, the program generates and verifieshypotheses on the disposition of a sequential modulating regionin a protein, and key characteristics of the region. In manualmode, users can generate and analyze their own hypotheses. Theprogram is implemented on IBM PC or compatible computers. Itis designed to be easily handled by the occasional computeruser and yet it is powerful enough for experienced professionals.ProAnal operation is demonstrated on the example of findingmodulating centers in a family of disintegrinsproteinsfrom snake venoms which inhibit fibrinogen interaction withplatelet receptors. In another example it is shown that theimmunogenicity of peptides is connected with their positivecharge. 相似文献
18.
The inhibitory effect of glucagon on exocrine pancreas has been the subject of controversial reports. On the other hand, oxyntomodulin (bioactive enteroglucagon or glucagon-37), a 37 amino acid peptide isolated from porcine lower intestine, has been shown to be 10–20 times more potent than glucagon in inhibiting gastric acid secretion in the rat. In view of this, the effect of glucagon and oxyntomodulin on basal and caerulein-stimulated pancreatic secretion has been studied, during re-introduction of pancreatic juice into duodenum, in the conscious rat provided with pancreatic and duodenal fistulas. A depression of pancreatic function was observed with both peptides on the three parameters studied: (volume of juice secreted, bicarbonate and protein output), either under basal conditions or during stimulation by caerulein. In all the experimental conditions used, oxyntomodulin was ca. ten times more potent than glucagon in its inhibitory effect. The fact that oxyntomodulin, as what is observed in the stomach, is one order of magnitude more potent than glucagon in inhibiting pancreatic secretion suggests that the biological mechanisms by which the peptides of the glucagon-family act on exocrine pancreas are similar, or related to that present at the gastric level. 相似文献
19.
Li JP Chang TM Chey WY 《American journal of physiology. Gastrointestinal and liver physiology》2001,280(4):G595-G602
5-Hydroxytryptamine (serotonin, 5-HT) is a hormone and neurotransmitter regulating gastrointestinal functions. 5-HT receptors are widely distributed in gastrointestinal mucosa and the enteric nervous system. Duodenal acidification stimulates not only the release of both 5-HT and secretin but also pancreatic exocrine secretion. We investigated the effect of 5-HT receptor antagonists on the release of secretin and pancreatic secretion of water and bicarbonate induced by duodenal acidification in anesthetized rats. Both the 5-HT(2) receptor antagonist ketanserin and the 5-HT(3) receptor antagonist ondansetron at 1-100 microg/kg dose-dependently inhibited acid-induced increases in plasma secretin concentration and pancreatic exocrine secretion. Neither the 5-HT(1) receptor antagonists pindolol and 5-HTP-DP nor the 5-HT(4) receptor antagonist SDZ-205,557 affected acid-evoked release of secretin or pancreatic secretion. None of the 5-HT receptor antagonists affected basal pancreatic secretion or plasma secretin concentration. Ketanserin or ondansetron at 10 microg/kg or a combination of both suppressed the pancreatic secretion in response to intravenous secretin at 2.5 and 5 pmol x kg(-1) x h(-1) by 55-75%, but not at 10 pmol x kg(-1) x h(-1). Atropine (50 microg/kg) significantly attenuated the inhibitory effect of ketanserin on pancreatic secretion but not on the release of secretin. These observations suggest that 5-HT(2) and 5-HT(3) receptors mediate duodenal acidification-induced release of secretin and pancreatic secretion of fluid and bicarbonate. Also, regulation of pancreatic exocrine secretion through 5-HT(2) receptors may involve a cholinergic pathway in the rat. 相似文献
20.
Physiological plasma concentrations of cholecystokinin stimulate pancreatic enzyme secretion and gallbladder contraction in man 总被引:1,自引:0,他引:1
P J Kerstens C B Lamers J B Jansen A J de Jong M Hessels J C Hafkenscheid 《Life sciences》1985,36(6):565-569
The present study was undertaken to determine whether infusion of cholecystokinin (CCK) to plasma concentrations comparable to those found after a meal stimulates pancreatic enzyme secretion and gallbladder contraction. Plasma CCK concentrations were measured by radioimmunoassay using antibody T204, which binds to all carboxyl-terminal CCK-peptides containing the sulfated tyrosine region. Ingestion of a standardized test meal in 7 normal subjects induced significant increases in plasma CCK from 2.0 +/- 0.2 pmol/l to levels between 4.6 +/- 0.6 and 7.3 +/- 1.0 pmol/l (p less than 0.05-p less than 0.0005). Infusion of 2.5 pmol/kg X h CCK 33 resulted in significant increases in plasma CCK from 2.0 +/- 0.2 to 3.9 +/- 0.3 pmol/l (p less than 0.0005). This infusion of CCK induced significant increases in trypsin secretion from 0.5 +/- 0.1 to 1.4 +/- 0.2 KU/15 min (p less than 0.005) and in bilirubin output from 1.6 +/- 0.7 to 30.3 +/- 8.0 mumol/15 min (p less than 0.05). It is concluded that physiological plasma concentrations of CCK stimulate pancreatic enzyme secretion and gallbladder contraction in man. 相似文献