DOCSLIB.ORG

Gastric Inhibitory Polypeptide (GIP)*

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

J Clin Pathol: first published as 10.1136/jcp.s1-8.1.31 on 1 January 1978. Downloaded from J. clin. Path., 33, Suppl. (Ass. Clin. Path.), 8, 31-37 Gastric inhibitory polypeptide (GIP) * D. L. SARSON From the Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS As long ago as 1930, Kosaka and Lim proposed a sample with 8. 0 M urea. Thus, this peak may humoral agent capable of inhibiting gastric acid represent a protein/peptide complex. secretion after a meal. They coined the term entero- (2) A large molecular form which may correspond gastrone. Using crude preparations of cholecysto- to either a 'big GIP' or a precursor pro-GIP. kinin-pancreozymin (CCK PZ) in dogs they were (3) A 5000 dalton molecular form. This peak elutes able to inhibit the acid secretion normally stimulated in the same position as porcine standard and by a meat meal or histamine. They went on to 1251-labelled GIP. experiment with duodenal extracts, prepared after The exact nature and properties of these different the instillation into the duodenum of olive oil, molecular species require further analysis to deter- and found a similar effect to that seen with crude mine which form or forms of GIP are biologically CCK PZ. The effects of similar crude preparations active. ofCCK PZ in the dog were confirmed Brown On the basis of several by and amino-acid sequence copyright. Pederson in 1970, but further purification of this homologies GIP has been placed in the classical material led to a diminution of the acid inhibitory secretin-glucagon-VIP family of peptides. Indeed effect (Brown and Pederson, 1970). In 1971, Brown and Dryburgh purified and sequenced this gastric inhibitory fraction and found it to be a polypeptide 30 quite distinct from other known peptide hormones. By virtue of its acid inhibitory properties they 20 http://jcp.bmj.com/ named it gastric inhibitory polypeptide, GIP. 10 Chemistry GIP consists of 43 amino-acid residues in a single .0 30. Jejunal extract U chain, with a molecular weight of 5105 daltons. The 20- amino-acid sequence is shown below. Residues which have been underlined correspond to sequence homo- 0 10 on September 27, 2021 by guest. Protected logies with other members of the secretin-VIP- E_ glucagon family of peptides. L J . jA. af J . '-.a Tyrl-Ala-Glu-Gly-Thr5-Phe-Ile- Ser-Asp-Tyr10- 30 Ser-Ile-Ala-Met-Asp15-Lys-Ile-Arg-Gln-Gln2O- Normal fasting plasma Asp-Phe-Val-Asn-Trp25-Leu-LeuAla-Gln-G]n3k 20 A Lys-Gly-Lys-Lys-Ser35-Asp - Trp - Lys - His- Asn40-Ile-Thr-Gln Chromatographic analysis of jejunal extracts and A ..AA _.it of serum taken after a mixed meal has shown that Protein Cytochrome C Insulin GIP Glucagon GIP exists in more than one molecular form (Brown 125J et al., 1975; Sarson et al., 1979). Three distinct peaks 3j of immunoreactive GIP have been shown (Fig. 1). Fc3onumbe 45 50 5 (1) A high molecular weight fraction which occurs Fraction number in the void volume. A significant reduction in this peak is seen following Fig. 1 Chromatographic analysis ofjejunal extract pretreatment of the andfasting plasma showing the peaks of *Now often referred to as glucose-dependent insulinotropic poly- immunoreactive GIP. The position ofseveral markers is peptide. indicated below the plasma extract. 1 J Clin Pathol: first published as 10.1136/jcp.s1-8.1.31 on 1 January 1978. Downloaded from 32 D. L. Sarson these structural similarities are mirrored effectively in shared pharmacological activities. Examples of properties common to these substances are inhibition of gastric acid secretion and the in vivo and in vitro release of insulin. CELLULAR LOCALISATION AND DISTRIBUTION The availability of suitable antisera to GIP has made it possible to localise the GIP-containing cells by indirect immunofluorescence studies. Work reported in 1973 by Polak and colleagues tentatively identified the GIP cell as residing in the middle layer of the upper intestinal mucosa. Recently the site of anti- GIP antiserum activity has been shown to be the K cell, previously classified by electron microscopy according to the appearance of its granules (Buffa et al., 1975). Radioimmunoassay of GIP in extracts of homo- genised gut tissue has confirmed these histochemical findings. Immunoreactive GIP (IR GIP) has been found to be distributed throughout the upper small intestine (Fig. 2), with the greatest concentration in the jejunal mucosa (Bloom et al., 1975). copyright. MEAS UREMENT The crude bioassay employed by Brown and co- workers in the course of purifying GIP is far too insensitive to detect the small quantities in the circulation released by physiological stimuli. This is only possible by the use of a sensitive and highly http://jcp.bmj.com/ specific radioimmunoassay. Several such assays have 0 1-1i been reported (Kuzio et al., 1974; Lauritsen and o 11-30 *>31 Moody, 1978; Morgan et al., 1978; Sarson et al., No of cells per rnm2 1979), but there appears to be little agreement between different authors with regard to basal and Fig. 2 Distribution of GIP in the gastrointestinal tract of man. The numbers denote the concentration of postprandial serum concentrations. In some cases immunoreactive GIP, and the shading denotes the ten-fold differences have been reported. frequency of GIP-containing cells. on September 27, 2021 by guest. Protected Several factors probably contribute to these differences. Primarily, the affinity of the antisera for completely clear. A possible factor is the presence of each different molecular form of IR GIP needs to be two tyrosine residues which may result in excessive determined, and also whether the forms measured incorporation of 126iodine. Another is oxidation of reflect biological activity. the methionine residue during iodination. The Secondly, but of equal importance, are the diffi- resulting damaged peptide is poorly recognised by the culties arising from the poor antigenicity of GIP, antisera and is unstable, with a short shelf life. and the need to conjugate it with a larger molecule. Some assayists have also noted non-specific inter- The latter procedure may lead to conformational ference by plasma, and plasma extraction techniques damage to the molecule, resulting in subsequent have been introduced. Some authors have even been problems in the assay. Moreover, the shortage ofpure tempted to set up their standard curves in buffer GIP has led to the use oflarge amounts ofimpure pre- devoid of plasma, thereby effectively hiding the parations for the raising of antisera. The major con- problem. In several cases GIP antibodies have also sequence of this is the production of a heterogeneous been shown to be rapidly dissociated from 125I-GIP population of antibodies with low specificity. by charcoal slurry. This has necessitated the use of Another common difficulty is the preparation of alcohol precipitation or double antibody separation the radio-labelled peptide with high specific activity techniques, though it is a feature generally found and full immunogenicity. The reason for this is not with low affinity antisera. J Clin Pathol: first published as 10.1136/jcp.s1-8.1.31 on 1 January 1978. Downloaded from Gastric inhibitory polypeptide (GIP) 33 In spite of the difficulties encc)untered with GIP Intravenous administration of these nutrients does radioimmunoassays and the differences in reported not elicit a GIP response. values of circulating hormone, thiere has been con- siderable agreement on the nature cDfthestimuli which INHIBITION OF GASTRIC ACID SECRETION release GIP. The results so far haive provided much GIP was originally discovered and named as the acid useful and exciting information 'with regard to the inhibitory fraction of crude CCK PZ. Its release by physiology and pathology of this new hormone. fat and glucose, which are both potent inhibitors ofgastric acid secretion, further suggested an 'entero- Physiology gastrone' role. Much of the initial work was carried out in dogs, in which a clear relationship between There have been several actions described for GIP inhibition of acid secretion and GIP release was and these are listed below. seen. Thus, infusions of porcine GIP, to attain (l) The inhibition of gastric acid secretion. circulating levels within the physiological range, (2) The inhibition of pepsin secretion. inhibited pentagastrin-stimulated acid secretion in (3) The inhibition of gastric motcDr activity. dogs with denervated fundic pouches (Pederson and (4) The stimulation of insulin release. Brown, 1972); there was a good dose/response (5) The stimulation of glucagon rrelease. relationship. The instillation of lipomul, a trigly- (6) The stimulation of the flow offjejunal water and ceride suspension, into the duodenum evoked a rise electrolytes. in circulating plasma IR GIP and a reduction in acid Some of these actions are nomv considered to be secretion ofthe order of70 %. However, the hydrogen pharmacological rather than ph3ysiological as they ion secretion returned to normal while the circulating are only seen with plasma concenitrations far higher GIP levels remained substantially raised. This than those encountered after natiural stimuli. Thus, differed from the effect of intravenous GIP, after the role of GIP in gastric acid inhibition and as an which acid secretion returned to control levels copyright. enteric releaser of insulin have cormmanded the most concurrently with the fall in GIP. It was suggested attention. that the triglyceride mixture released the larger The ingestion of a mixed mteal results in an molecular form of GIP which had no enterogastrone increase of circulating GIP concentration, the peak activity (Pederson et al., 1978). occurring after about 45 minutes. Separation of the The role of GIP in the inhibition of acid secretion meal into its constituent nutrients showed that the in man is less well understood than in dogs, and has most potent stimuli to GIP release are carbohydrates given rise to conflicting reports.
Recommended publications
  • Coffee and Its Effect on Digestion

    Coffee and Its Effect on Digestion

    Expert report Coffee and its effect on digestion By Dr. Carlo La Vecchia, Professor of Medical Statistics and Epidemiology, Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy. Contents 1 Overview 2 2 Coffee, a diet staple for millions 3 3 What effect can coffee have on the stomach? 4 4 Can coffee trigger heartburn or GORD? 5 5 Is coffee associated with the development of gastric or duodenal ulcers? 6 6 Can coffee help gallbladder or pancreatic function? 7 7 Does coffee consumption have an impact on the lower digestive tract? 8 8 Coffee and gut microbiota — an emerging area of research 9 9 About ISIC 10 10 References 11 www.coffeeandhealth.org May 2020 1 Expert report Coffee and its effect on digestion Overview There have been a number of studies published on coffee and its effect on different areas of digestion; some reporting favourable effects, while other studies report fewer positive effects. This report provides an overview of this body of research, highlighting a number of interesting findings that have emerged to date. Digestion is the breakdown of food and drink, which occurs through the synchronised function of several organs. It is coordinated by the nervous system and a number of different hormones, and can be impacted by a number of external factors. Coffee has been suggested as a trigger for some common digestive complaints from stomach ache and heartburn, through to bowel problems. Research suggests that coffee consumption can stimulate gastric, bile and pancreatic secretions, all of which play important roles in the overall process of digestion1–6.
  • John H. Northrop

    John H. Northrop

    J OHN H . N ORTHROP T h e preparation of pure enzymes and virus proteins* Nobel Lecture, December 12, 1946 The problem of the chemical nature of the substances which control the reactions occurring in living cells has been a subject of research, and also of controversy, for nearly two hundred years. Before the eighteenth century these reactions were considered as "vital processes", outside the realm of experimental science. The work of Spallanzani, Payen and Persoz, Schwann, Kühne, and finally Buchner proved that many of these reactions could take place without living cells and were probably caused by the presence of small amounts of unstable and active substances, which Kühne called "enzymes". Berzelius, a century ago, pointed out that these enzymes were similar to the catalysts of the chemist and suggested that they be considered as special catalysts formed by the cells. This hypothesis was far ahead of its time and met with great opposition, since many workers considered that enzyme reac- tions differed qualitatively from ordinary chemical reactions. The work of Tamman, Arrhenius, Henri, Michaelis, Nelson, von Euler, Willstätter, War- burg, and other chemists, however, has shown that Berzelius’ viewpoint was correct and enzyme reactions are now considered a special kind of catalysis which does not differ qualitatively from other catalytic reactions. While the study of enzyme reactions made rapid progress all attempts to isolate an enzyme and so determine its chemical nature were unsuccessful until recently. The early workers were of the opinion that enzymes were probably pro- teins and in 1896 Pekelharing isolated a protein from gastric juice which he considered to be the enzyme pepsin.
  • DUAL ROLE of CATHEPSIN D: LIGAND and PROTEASE Martin Fuseka, Václav Větvičkab

    DUAL ROLE of CATHEPSIN D: LIGAND and PROTEASE Martin Fuseka, Václav Větvičkab

    Biomed. Papers 149(1), 43–50 (2005) 43 © M. Fusek, V. Větvička DUAL ROLE OF CATHEPSIN D: LIGAND AND PROTEASE Martin Fuseka, Václav Větvičkab* a Institute of Organic Chemistry and Biochemistry, CAS, Prague, Czech Republic, and b University of Louisville, Department of Pathology, Louisville, KY40292, USA, e-mail: [email protected] Received: April 15, 2005; Accepted (with revisions): June 20, 2005 Key words: Cathepsin D/Procathepsin D/Cancer/Activation peptide/Mitogenic activity/Proliferation Cathepsin D is peptidase belonging to the family of aspartic peptidases. Its mostly described function is intracel- lular catabolism in lysosomal compartments, other physiological effect include hormone and antigen processing. For almost two decades, there have been an increasing number of data describing additional roles imparted by cathepsin D and its pro-enzyme, resulting in cathepsin D being a specific biomarker of some diseases. These roles in pathological conditions, namely elevated levels in certain tumor tissues, seem to be connected to another, yet not fully understood functionality. However, despite numerous studies, the mechanisms of cathepsin D and its precursor’s actions are still not completely understood. From results discussed in this article it might be concluded that cathepsin D in its zymogen status has additional function, which is rather dependent on a “ligand-like” function then on proteolytic activity. CATHEPSIN D – MEMBER PRIMARY, SECONDARY AND TERTIARY OF ASPARTIC PEPTIDASES FAMILY STRUCTURES OF ASPARTIC PEPTIDASES Major function of cathepsin D is the digestion of There is a high degree of sequence similarity among proteins and peptides within the acidic compartment eukaryotic members of the family of aspartic peptidases, of lysosome1.
  • Hydrolysis of -Lactalbumin by Chymosin and Pepsin. Effect Of

    Hydrolysis of -Lactalbumin by Chymosin and Pepsin. Effect Of

    Hydrolysis of α-lactalbumin by chymosin and pepsin. Effect of conformation and pH G. Miranda, G. Hazé, Non Renseigné To cite this version: G. Miranda, G. Hazé, Non Renseigné. Hydrolysis of α-lactalbumin by chymosin and pepsin. Effect of conformation and pH. Le Lait, INRA Editions, 1989, 69 (6), pp.451-459. hal-00929176 HAL Id: hal-00929176 https://hal.archives-ouvertes.fr/hal-00929176 Submitted on 1 Jan 1989 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Lait (1989) 69. 451-459 451 © Elsevier/INRA Original article Hydrolysis of œ-lactalburnin by chymosin and pepsin. Effect of conformation and pH G. Miranda, G. Hazé, P.Scanff and J.P.Pélissier INRA, station de recherches laitières, 78350 Jouy-en-Josas, France (received 21 March 1989. accepted 26 June 1989) Summary - The correlation between change of conformation of a-Iactalbumin and its degradation by gastric enzymes was verified. With citrate buffer (0.1 M), the modification of a-Iactalbumin confor- mation occurred when the pH value was below pH 4.0. This conformational change was influenced by buffer composition and ionic strength. However, the presence of EDTA in the butter did not modi- fy the pH value at which the change of conformation of the protein occurred.
  • Structure of the Human Renin Gene

    Structure of the Human Renin Gene

    Proc. Nati. Acad. Sci. USA Vol. 81, pp. 5999-6003, October 1984 Biochemistry Structure of the human renin gene (hypertension/aspartyl proteinase/nucleotide sequence/splice junction) HITOSHI MIYAZAKI*, AKIYOSHI FUKAMIZU*, SHIGEHISA HIROSE*, TAKASHI HAYASHI*, HITOSHI HORI*, HIROAKI OHKUBOt, SHIGETADA NAKANISHIt, AND KAZUO MURAKAMI** *Institute of Applied Biochemistry, University of Tsukuba, Ibaraki 305, Japan; and tInstitute for Immunology, Kyoto University Faculty of Medicine, Kyoto 606, Japan Communicated by Leroy Hood, June 27, 1984 ABSTRACT The human renin gene was isolated from a between the intron-exon organization of the gene and the Charon 4A human genomic library and characterized. The tertiary structure of the protein. gene spans about 11.7 kilobases and consists of 10 exons and 9 introns that map at points that could be variable surface loops MATERIALS AND METHODS of the enzyme. The complete coding regions, the 5'- and 3'- Materials. All restriction enzymes were obtained from flanking regions, and the exon-intron boundaries were se- either New England Biolabs or Takara Shuzo (Kyoto, Ja- quenced. The active site aspartyl residues Asp-38 and Asp-226 pan). Escherichia coli alkaline phosphatase and T4 DNA li- are encoded by the third and eighth exons, respectively. The gase were from Takara Shuzo. [_y-32P]ATP (>5000 Ci/mmol; extra three amino acids (Asp-165, Ser-166, Glu-167) that are 1 Ci = 37 GBq) and [a-32P]dCTP (=3000 Ci/mmol) were not present in mouse renin are encoded by the separate sixth from Amersham. exon, an exon as small as 9 nucleotides. The positions of the Screening. A human genomic library, prepared from partial introns are in remarkable agreement with those in the human Alu I and Hae III digestion and ligated into the EcoRI arms pepsin gene, supporting the view that the genes coding for of the X vector Charon 4A, was kindly provided by T.
  • Somatostatin Inhibits Gastric Acid Secretion After Gastric Mucosal Prostaglandin Synthesis Inhibition by Indomethacin in Man

    Somatostatin Inhibits Gastric Acid Secretion After Gastric Mucosal Prostaglandin Synthesis Inhibition by Indomethacin in Man

    Gut: first published as 10.1136/gut.26.11.1189 on 1 November 1985. Downloaded from Gut, 1985, 26, 1189-1191 Somatostatin inhibits gastric acid secretion after gastric mucosal prostaglandin synthesis inhibition by indomethacin in man M H MOGARD, V MAXWELL, T KOVACS, G VAN DEVENTER, J D ELASHOFF, T YAMADA, G L KAUFFMAN JR, AND J H WALSH From the Centerfor Ulcer Research and Education, VA Wadsworth MedicallSurgical Services and UCLA, LosAngeles, California, USA. SUMMARY The inhibitory effect of indomethacin, 200+200 mg administered per os over 24 hours, on the prostaglandin E2 generative capacity of gastric mucosal tissue was determined in healthy male volunteers. The effect of prostaglandin synthesis inhibition on somatostatin induced suppression of food-stimulated acid secretion was tested. Peptone meal stimulated acid secretion was quantified in five healthy volunteers by intragastric titration with and without indomethacin pretreatment. Somatostatin doses of 200, 400, and 800 pmol/kg/h each significantly inhibited the peptone stimulated acid output. Indomethacin treatment, resulting in 90% inhibition of prostaglandin E2 synthesis, did not affect glucose- or peptone-stimulated acid output or modify the inhibitory action of somatostatin. Clinically, acid inhibition by somatostatin has been used to treat bleeding peptic ulcers. Ulcer haemorrhage may be preceded by an excessive use of drugs that inhibit prostaglandin synthesis such as aspirin or other non-steroidal anti-inflammatory agents. Recent observations in the rat indicate that prostaglandins mediate the inhibitory action of somatostatin on gastric acid secretion. The present results suggest that prostaglandins are not http://gut.bmj.com/ required for inhibition of gastric acid secretion by somatostatin in man.
  • Proteolytic Cleavage—Mechanisms, Function

    Proteolytic Cleavage—Mechanisms, Function

    Review Cite This: Chem. Rev. 2018, 118, 1137−1168 pubs.acs.org/CR Proteolytic CleavageMechanisms, Function, and “Omic” Approaches for a Near-Ubiquitous Posttranslational Modification Theo Klein,†,⊥ Ulrich Eckhard,†,§ Antoine Dufour,†,¶ Nestor Solis,† and Christopher M. Overall*,†,‡ † ‡ Life Sciences Institute, Department of Oral Biological and Medical Sciences, and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada ABSTRACT: Proteases enzymatically hydrolyze peptide bonds in substrate proteins, resulting in a widespread, irreversible posttranslational modification of the protein’s structure and biological function. Often regarded as a mere degradative mechanism in destruction of proteins or turnover in maintaining physiological homeostasis, recent research in the field of degradomics has led to the recognition of two main yet unexpected concepts. First, that targeted, limited proteolytic cleavage events by a wide repertoire of proteases are pivotal regulators of most, if not all, physiological and pathological processes. Second, an unexpected in vivo abundance of stable cleaved proteins revealed pervasive, functionally relevant protein processing in normal and diseased tissuefrom 40 to 70% of proteins also occur in vivo as distinct stable proteoforms with undocumented N- or C- termini, meaning these proteoforms are stable functional cleavage products, most with unknown functional implications. In this Review, we discuss the structural biology aspects and mechanisms
  • Pepsin Certificate of Analysis 9PIV1959

    Pepsin Certificate of Analysis 9PIV1959

    Certificate of Analysis Pepsin: Part No. Size Part# 9PIV1959 V195A 250mg Revised 8/16 Description: Pepsin preferentially cleaves at the C-terminus of phenylalanine, leucine, tyrosine and tryptophan (1–4). This protease can be used alone or in combination with other proteases for protein analysis by mass spectrometry and other applications. Biological Source: Porcine stomach . Molecular Weight: 34.6kDa . Form: Lyophilized . Storage Conditions: See the Product Information Label for storage conditions and expiration date. *AF9PIV19590816V1959* Optimal pH: 1.0–3.0 (4–6). AF9PIV19590816V1959 Activators: Hydrochloric acid (HCl), trifluoroacetic acid (TFA). Inactivators: pH greater than 6.0. Usage Notes: 1. Resuspend Pepsin in double-distilled water (pH 5.5 or lower) to a final concentration of 1mg/ml. Store reconstituted Pepsin at 4°C for up to 1 month. 2. Specificity for cleavage at Phe and Leu is best at pH 1.0 and decreased above pH 2.0. Pepsin irreversibly inactivates above pH 6.0. Promega Corporation 2800 Woods Hollow Road Madison, WI 53711-5399 USA Telephone 608-274-4330 Toll Free 800-356-9526 Fax 608-277-2516 Quality Control Assays Internet www.promega.com This lot passes the following Quality Control specifications: Activity: Digestion reactions using insulin as a substrate are performed at a protease:substrate ratio of 1:20 and analyzed by PRODUCT USE LIMITATIONS, WARRANTY, DISCLAIMER reverse-phase HPLC. Intact substrate is undetectable after incubation for 15 minutes at 37°C. Promega manufactures products for a number of intended uses. Please refer to the product label for the intended use statements for specific products. Usage Information on Back Promega products contain chemicals which may be harmful if misused.
  • Cleavage of Honeybee Prepromelittin by an Endoprotease from Rat Liver Microsomes: Identification of Intact Signal Peptide

    Cleavage of Honeybee Prepromelittin by an Endoprotease from Rat Liver Microsomes: Identification of Intact Signal Peptide

    Proc. Natl. Acad. Sci. USA Vol. 79, pp. 2260-2263, April 1982 Biochemistry Cleavage of honeybee prepromelittin by an endoprotease from rat liver microsomes: Identification of intact signal peptide (precursor processing/signal peptidase/membrane protein/melittin) CHRISTA MOLLAY, ULRIKE VILAS, AND GUNTHER KREIL Institute for Molecular Biology, Austrian Academy of Sciences, Billrothstrasse 11, A5020 Salzburg, Austria Communicated by Paul D. Boyer, January 19, 1982 ABSTRACT It has previously been shown that rat liver mi- tivities, on a sucrose-deoxycholate gradient. This endoprotease crosomes contain a proteolytic enzyme that cleaves honeybee pre- cleaves prepromelittin at a single peptide bond, the pre- promelittin to yield promelittin. This enzyme has now been fur- pro junction. The-present communication describes the isola- ther purified by centrifugation on a sucrose-deoxycholate gradient tion ofthe second reaction product, intact signal peptide, from and then reconstituted into phospholipid vesicles. Incubation of such in vitro assays. prepromelittin with vesicles in the presence of melittin yields, in addition to promelittin, a hydrophobic peptide. The latter could be isolated by extraction with 1-butanol and paper electrophoresis MATERIALS AND METHODS in 30% formic acid and was shown to be intact signal peptide by analysis of peptic fragments and automated Edman degradation. Tritium-labeled amino acids ofthe highest specific activity cur- The microsomal enzyme is thus an endoprotease that hydrolyzes rently available were purchased from the Radiochemical Centre prepromelittin exclusively at the pre-pro junction. The precision (Amersham, England). Phospholipids were obtained from Lipid of this cleavage of an insect preprotein by a rat liver enzyme in- Products (Nutfield Nurseries, England), synthetic dipeptides dicates that we are dealing with the ubiquitous eukaryotic signal were from Bachem AG (Bubendorf, Switzerland), and other peptidase.
  • Lecture Series Gastrointestinal Tract

    Lecture Series Gastrointestinal Tract

    Lecture series Gastrointestinal tract Professor Shraddha Singh, Department of Physiology, KGMU, Lucknow INNERVATION OF GIT • 1.Intrinsic innervation-1.Myenteric/Auerbach or plexus Local 2.Submucosal/Meissners plexus 2.Extrinsic innervation-1.Parasympathetic or -2.Sympathetic Higher centre Enteric Nervous System - Lies in the wall of the gut, beginning in the esophagus and - extending all the way to the anus - controlling gastrointestinal movements and secretion. - (1) an outer plexus lying between the longitudinal and circular muscle layers, called the myenteric plexus or Auerbach’s plexus, - controls mainly the gastrointestinal movements - (2) an inner plexus, called the submucosal plexus or Meissner’s plexus, that lies in the submucosa. - controls mainly gastrointestinal secretion and local blood flow Enteric Nervous System - The myenteric plexus consists mostly of a linear chain of many interconnecting neurons that extends the entire length of the GIT - When this plexus is stimulated, its principal effects are - (1) increased tonic contraction, or “tone,” of the gut wall, - (2) increased intensity of the rhythmical contractions, - (3) slightly increased rate of the rhythmical contraction, - (4) increased velocity of conduction of excitatory waves along the gut wall, causing more rapid movement of the gut peristaltic waves. - Inhibitory transmitter - vasoactive intestinal polypeptide (VIP) - pyloric sphincter, sphincter of the ileocecal valve Enteric Nervous System - The submucosal plexus is mainly concerned with controlling function within the inner wall - local intestinal secretion, local absorption, and local contraction of the submucosal muscle - Neurotransmitters: - (1) Ach (7) substance P - (2) NE (8) VIP - (3)ATP (9) somatostatin - (4) 5 – HT (10) bombesin - (5) dopamine (11) metenkephalin - (6) cholecystokinin (12) leuenkephalin Higher centre innervation - the extrinsic sympathetic and parasympathetic fibers that connect to both the myenteric and submucosal plexuses.
  • Protease Inhibitors in Human Milk

    Protease Inhibitors in Human Milk

    Pediat. Res 13: 969-972 (1979) Chymotrypsin protease inhibi- elastase tors human milk trypsin Protease Inhibitors in Human Milk TOR LINDBERG Departments of Pediatrics and Experimental Research, Malmo General Hospital, University of Lund, Malmo, Sweden Summary standard serum for the measurements of the concentration of a,- antitrypsin and antichymotrypsin were gifts of Dr P. Fernlund, Protease inhibitors (inhibiting trypsin, chymotrypsin, and elas- Department of Clinical Chemistry, Malmo General Hospital. A tase) were demonstrated in human milk from birth to 4 months standard pool of serum from 1000 donors was regarded as 100'70 after delivery. No pepsin inhibitor was found. The protease inhib- = about 1.35 g a,-antitrypsin/liter and 0.5 g antichymotrypsin/ itors were localized in the al-region-inhibiting trypsin, chymo- liter. trypsin, and elastase-and in a more cathodal region-inhibiting Chemicals: Agarose (Miles-Seravac, Maidenhead, England) ca- chymotrypsin-in agarose gel electrophoresis of human milk. al- sein (BDH), elastin (Worthington), N-benzoyl-DL-arginine-p-ni- antitrypsin and antichymotrypsin were demonstrated by crossed troanilide (BAPNA) (Sigma), bovine trypsin (EC 3.4.4.4.) (Fluka), immunoelectrophoresis. Electroimmunoassay showed the concen- a-chymotrypsin (EC 3.4.4.5) (Fluka), pepsin (EC 3.4.23.1) (Fluka), tration of a,-antitrypsin in 1st day milk to be 109% and the and elastase (EC 3.4.4.7) (Sigma). concentration of antichymotrypsin was 116% of that of adult serum. The concentrations d&;eased during the 1st wk; from 1 wk to 4 months they were 1.6% for a,-antitrypsin and 3.84% for METHODS antichymotrypsin of those of adult serum.
  • A History of Gastric Secretion and Digestion a History of Gastric Secretion and Digestion Experimental Studies to 1975

    A History of Gastric Secretion and Digestion a History of Gastric Secretion and Digestion Experimental Studies to 1975

    A History of Gastric Secretion and Digestion A History of Gastric Secretion and Digestion Experimental Studies to 1975 HORACE W. DAVENPORT William Beaumont Professor of Physiology Emeritus The University of Michigan Springer New Y ork 1992 Copyright © 1992 by the American Physiological Society Originally published by American Physiological Society in 1992 Softcoverreprint of the bardeover 1st edition 1992 All rights reserved. No partoftbis publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission ofOxford University Press. Library ofCongress Cataloging-in-Publication Data Davenport, Horace Willard, 1912- A history of gastric secretion and digestion : experimental studiesto 1975 I Horace W. Davenport. p. cm. lncludes bibliographical references and index. ISBN 978-1-4614-7602-3 (eBook) DOI 10.1007/978-1-4614-7602-3 I. Gastroenterology-History. 2. Gastric-Secretion-Research-History. 3. Digestion-Research-History. I. Title. [DNLM: I. Digestion. 2. Gastric Acid-secretion. 3. Gastroenterology-history. 4. Research-history. 5. Stomach-chemistry. 6. Stomach-physiology. Wlll.l D247h] QP145.D325 1992 612.3'2'072-dc20 DNLM/DLC for Library ofCongress 91-31832 987654321 For Charles F. Code, known to every gastroenterologist as "Charlie Code" and as their preeminent physiologist for the last fifty years Preface For centuries men speculated about the process of gastric digestion, but Iate in the eighteenth and early in the nineteenth centuries physiologists, both physicians and laymen, began to accumulate experimental evidence about its nature. At the same time, others discovered that the stomach is capable of secreting a strong mineral acid, and the questions of how that secretion is produced and how it is controlled became enduring problems.