DOCSLIB.ORG

The Endocrine Versatility of the Gut: General and Evolutionary Aspects of the Active Peptides of the Gastrointestinal Tract

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Endocrine Versatility of the Gut: General and Evolutionary Aspects of the Active Peptides of the Gastrointestinal Tract J Clin Pathol: first published as 10.1136/jcp.s1-8.1.1 on 1 January 1978. Downloaded from J. clin. Path., 33, Suppl. (Ass. Clin. Path.), 8, 1-6 The endocrine versatility of the gut: general and evolutionary aspects of the active peptides of the gastrointestinal tract G. J. DOCKRAY From the Physiological Laboratory, University ofLiverpool, Brownlow Hill, PO Box 147, Liverpool L69 3BX Recent years have seen an unprecedented expansion system, and other peptides previously identified in of interest in the gastrointestinal endocrine system brain have since been found in the gut. These that shows no signs of abating. In large measure this developments raise questions of fundamental im- awakening can be attributed to the chemical studies portance about the interrelationships ofthe brain-gut that have resulted in the isolation and elucidation of peptides and their roles in health and disease that, structure of a wide variety of biologically active gut taken together, point to the need for a re-evaluation peptides (Gregory and Tracy, 1975; Mutt, 1976). of the system of peptide messengers as a whole. An The availability of highly purified preparations of important aspect of such an analysis is the extent to these peptides has made possible detailed studies of which the chemical and functional relationships of their effects and mode of action at the cellular level. these peptides can be accounted for in evolutionary In addition, it has become possible to apply immuno- terms. The relevance of this approach is emphasised copyright. chemical methods of analysis that have helped to by the similarity in structure of groups of brain-gut reveal the cellular origins of the peptides and have peptides that suggest a shared ancestry, both of the allowed their estimation in blood and tissue extracts. molecules in question, and of the entire system of Several unexpected findings have emerged from these neuronal and hormonal peptides. studies. For example, it now seems possible that some of the peptides produced by gut endocrine Interrelationships of nerves and endocrine cells are the stream, but cells not secreted into blood http://jcp.bmj.com/ rather act locally by diffusion to their targets through At least eight peptides have been reported to occur the extracellular space (paracrine effects). Further- in mammalian gut endocrine cells and in central or more, it is now clear that many of the active peptides peripheral nerve fibres (Table 1). Only substance P in gut extracts originate not just in gut endocrine and neurotensin have been isolated from both cells but also in nerve fibres. Peptides of the en- tissues (Leeman et al., 1977); much of the evidence teric plexuses are also found in the central nervous for the distribution of the other peptides rests on on October 2, 2021 by guest. Protected Peptide Gut Gut Brain Amphibian Other tissues nerves endocrine cells skin glands + + + GastrinCholecystokn + + + f Cacrulein (Phe-Met-Arg-Phe-NH2 in mollusc nerves) VIP + + + _ Glucagon - + - - Vertebrate pancreas GIP - + - - Secretin - + - - Motilin - + - - Somatostatin + + + - Protochordate gut endocrine cells TRF ? ? + + Insect ganglia Bombesin + + + + Substance P + + + Physaelemin Eledoisin in cephalopod salivary gland Neurotensin - + + Xenopsin Enkephalin + + + Chymodenin ? ? ACTH - + + - Vertebrate pituitary Table 1 Distribution ofpeptides found in vertebrate gut extracts + Identified by isolation and/or immunochemical methods; - absent, or not yet reported; ? present in extracts but cellular origin uncertain. 1 J Clin Pathol: first published as 10.1136/jcp.s1-8.1.1 on 1 January 1978. Downloaded from 2 G. J. Dockray radioimmunoassay or immunocytochemistry, and thus one of the earliest forms of extracellular the possibility cannot be excluded that these sub- control to be mediated by peptides. stances exist as distinct but cross-reacting molecules On present evidence, peptide-secreting glandular in the brain and gut. As yet, cellular aspects of endocrine cells appear to be absent from the lower synthesis and secretion have been studied for only a metazoans, so that, in a sense, peptidergic neurones few peptides, but the balance of evidence favours can be considered ancestral to the endocrine cells the view that both hormonal and neuronal peptides of higher species. This need not imply direct are synthesised initially as large precursors which evolutionary descent of endocrine cells from are sequestered into secretory granules or vesicles, peptidergic neurones, although Pearse (1975) has converted by proteolytic and other enzymes to presented the evidence for this case. The ability to yield the active peptide, and are then released by produce and secrete active polypeptides occurs exocytosis or a related process. There may also be widely throughout both vertebrates and inverte- similarities in the electrical excitability of nerves and brates. For example, substance P is present in endocrine cells (Tischler et al., 1977). The differences mammalian nerves and gut enterochromaffin cells; between neuronal and hormonal peptides can there- in some amphibian species there are also high fore be seen to lie largely in the mode of their delivery concentrations of substance P-like peptides (physa- to target cells: on the one hand classical neurotrans- laemin) in skin, and a related peptide (eledoisin) has mitters diffuse across a synapse to act at a post- been isolated from the salivary gland of the cepha- synaptic site, and on the other hand hormones are lopod mollusc, Eledone. The wide distribution of released into the blood stream and so transported substance P-like peptides is not unique, and other to their targets. However, between these two ex- groups of peptides, such as those related to brady- tremes there are a variety of intermediate situations. kinin, also exhibit a wide distribution. In mammals, For example, some nerves, notably those associated bradykinin is generated in the peripheral circulation with the hypothalamus and neurohypophysis, by the action of proteolytic enzymes on a precursor copyright. secrete hormonal peptides directly into the blood protein produced in the liver, but related peptides stream. Other neuronal peptides are apparently not again occur in high concentrations in the skin of released either at synapses or capillaries, but may some amphibia, as well as in the venom secretion of nevertheless mediate nerve-nerve interactions with certain wasps (Bertaccini, 1976). Both examples slower onset and over longer periods than is gener- serve to illustrate the fact that related active peptides ally associated with classical neurotransmitters or their precursors can be found in a variety of (Barker, 1977). Similarly, it is thought that in the quite distinct systems with no obvious phylogenetic gut some endocrine cells might release peptides or functional relationships. Conceivably, the re- http://jcp.bmj.com/ which diffuse to, and act on, adjacent mucosal cells lated peptides of these diverse systems may have in a local or paracrine mode of regulation (Pearse arisen by a process of convergent evolution. It et al., 1977). Thus, there is no straightforward seems more reasonable to suppose, however, that distinction to be made between the mode of action these and probably other peptides were established of neuronal and hormonal peptides; instead there early in evolution and have since been strongly is an almost continuous spectrum between true conserved. Obviously, active peptides form only one hormones on the one hand and true neurotrans- link in a chain of communication that necessarily on October 2, 2021 by guest. Protected mitters on the other. includes other elements, such as appropriate target The evolutionary origins of peptides that function organ receptors and postreceptor transducing as extracellular molecular messengers are still mechanisms. Once established, the capacity to uncertain, and are in any case part of a larger employ a peptide as a molecular messenger might be problem that includes other aspects of cell-cell drawn upon independently by systems as different interaction, such as the origins of the regulation of as brain and gut by virtue of changes in the pattern growth and differentiation in multicellular organisms. of gene expression in these tissues. This is not There is evidence that nerves specialised for the particularly surprising for there are obvious ad- secretion of peptides, so called neurosecretory vantages to be gained by deploying in more than one neurones, are present in the most primitive of meta- biological context a single system of extracellular zoans (the coelenterates) and so can be considered communication molecules, for which the necessary an ancient feature established early in the evolution genetic information is already available. Set in this of nervous systems (Scharrer, 1978). The coelenter- light the dual distribution of peptides in gut and ate neuropeptides are thought to control growth and brain can be seen as an act of biological economy development, and since there is no circulatory or conservation. system in these animals they must presumably The dual function of a molecule as both hormone diffuse to their targets. Paracrine-like regulation is and neurotransmitter is not particularly novel, the J Clin Pathol: first published as 10.1136/jcp.s1-8.1.1 on 1 January 1978. Downloaded from The endocrine versatility of the gut 3 catecholamines being a well known case in point. (Gnathostomata) by over 500 million years of The successful application of the same messenger in evolution. The
Load more

Recommended publications
  • Amylase Release from Rat Parotid Gland Slices C.L
    Br. J. P!harmnic. (1981) 73, 517-523 THE EFFECTS OF SUBSTANCE P AND RELATED PEPTIDES ON a- AMYLASE RELEASE FROM RAT PAROTID GLAND SLICES C.L. BROWN & M.R. HANLEY MRC Neurochemical Pharmacology Unit, Medical Research Council Centre, Medical School, Hills Road, Cambridge CB2 2QH 1 The effects of substance P and related peptides on amylase release from rat parotid gland slices have been investigated. 2 Supramaximal concentrations (1 F.M) of substance P caused enhancement of amylase release over the basal level within 1 min; this lasted for at least 40 min at 30°C. 3 Substance P-stimulated amylase release was partially dependent on extracellular calcium and could be inhibited by 50% upon removal of extracellular calcium. 4 Substance P stimulated amylase release in a dose-dependent manner with an ED50 of 18 nm. 5 All C-terminal fragments of substance P were less potent than substance P in stimulating amylase release. The C-terminal hexapeptide of substance P was the minimum structure for potent activity in this system, having 1/3 to 1/8 the potency of substance P. There was a dramatic drop in potency for the C-terminal pentapeptide of substance P or substance P free acid. Physalaemin was more potent than substance P (ED50 = 7 nM), eledoisin was about equipotent with substance P (ED5o = 17 nM), and kassinin less potent than substance P (ED50 = 150 nM). 6 The structure-activity profile observed is very similar to that for stimulation of salivation in vivo, indicating that the same receptors are involved in mediating these responses.
    [Show full text]
  • Intracerebroventricular Responses to Neuropeptide Y in the Antagonists
    British Journal of Pharmacology (1996) 117, 241-249 B 1996 Stockton Press All rights reserved 0007-1188/96 $12.00 9 Intracerebroventricular responses to neuropeptide y in the conscious rat: characterization of its receptor with selective antagonists Pierre Picard & 'Rejean Couture Department of Physiology, Faculty of Medicine, Universite de Montreal, C.P. 6128, Succursale Centre-Ville, Montreal, Quebec, Canada H3C 3J7 1 The cardiovascular and behavioural effects elicited by the intracerebroventricular (i.c.v.) administration of neuropeptide y (NPy) in the conscious rat were assessed before and 5 min after i.c.v. pretreatment with antagonists selective for NKI (RP 67,580), NK2 (SR 48,968) and NK3 (R 820) receptors. In addition, the central effects of NPy before and after desensitization of the NK, and NK2 receptors with high doses of substance P (SP) and neurokinin A (NKA) were compared. 2 Intracerebroventricular injection of NPy (10-780 pmol) evoked dose- and time-dependent increases in mean arterial blood pressure (MAP), heart rate (HR), face washing, head scratching, grooming and wet-dog shake behaviours. Similar injection of vehicle or 1 pmol NPy had no significant effect on those parameters. 3 The cardiovascular and behavioural responses elicited by NPy (25 pmol) were significantly and dose- dependently reduced by pretreatment with 650 pmol and 6.5 nmol of SR 48,968. No inhibition of NPy responses was observed when 6.5 nmol of RP 67,580 was used in a similar study. Moreover, the prior co-administration of SR 48,968 (6.5 nmol) and RP 67,580 (6.5 nmol) with or without R 820 (6.5 nmol) did not reduce further the central effects of NPy and significant residual responses (30-50%) remained.
    [Show full text]
  • Back Matter (PDF)
    MOLECULAR PHARMACOLOGY 26:605-609 AUTHOR INDEX FOR VOLUME 26 A berg, Aaron, Watanabe, Kyoichi A., Fox, Jack J., and Philips, Frederick S. Metabolic Competition Studies of 2’-Fluoro-S-iodo-l- Albengres, Edith. See Urien, Riant, Brioude, and Tillement, 322 f3-D-arabinofuranosylcytosine in Vero Cells and Herpes Simplex Albuquerque, E. X. See Aracava, Ikeda, Daly, and Brooks, 304 Type 1-Infected Vero Cells, 587 See Ikeda, Aronstam, Daly, and Aracava, 293 Christie, Nelwyn T. See Cantoni, Swann, Drath, and Costa, 360 Ambler, S. Kelly, Brown, R. Dale, and Taylor, Palmer. The Chrivia, John. See Bolger, Dionne, Johnson, and Taylor, 57 Relationship between Phosphatidylinositol Metabolism and Mobili- Colacino, Joseph M. See Chou, Lopez, Feinberg, Watanabe, Fox, and zation of Intracellular Calcium Elicited by Alpha,-Adrenergic Recep- Philips, 587 tar Stimulation in BC3H-1 Muscle Cells, 405 Collins, Sheila, and Marletta, Michael A. Carcinogen-Binding Aracava, Y. Ikeda, S. R., Daly, J. W., Brookes, N., and Albu- Proteins: High-Affinity Binding Sites for Benzo[ajpyrene in Mouse querque, E. X. Interactions of Bupivacaine with Ionic Channels of Liver Distinct from the Ah Receptor, 353 the Nicotonic Receptor: Analysis of Single-Channel Currents, 304 Cooper, Dermot M. F. See Sadler and Mailer, 526 See Ikeda, Aronstam, Daly, and Albuquerque, 293 Corbett, Michael D. See Doerge, 348 Aronstam, R. S. See Ikeda, S. R. , Daly, J. W., Aracava, Y. , and Cormier, Ethel. See Jordan, Lieberman, Koch, Bagley, and Ruenitz, Albuquerque, E. X. , 293 272 Aub, Debra L. See Putney, McKinney, and Leslie, 261 Costa, Erminio. See Quach, Tang, Kageyama, Mocchetti, Guidotti, Meek, and Schwartz, 255 B Costa, Max.
    [Show full text]
  • The Vanilloid Receptor and Hypertension1
    Acta Pharmacologica Sinica 2005 Mar; 26 (3): 286–294 Invited review The vanilloid receptor and hypertension1 Donna H WANG2 Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI 48825, USA Key words Abstract TRP family; afferent neurons; capsaicin; Mammalian transient receptor potential (TRP) channels consist of six related pro- calcitonin gene-related peptide; substance P; tein sub-families that are involved in a variety of pathophysiological function, and vanilloid receptor; renin-angiotensin- aldosterone system; endothelin, sympathetic disease development. The TRPV1 channel, a member of the TRPV sub-family, is nervous system; salt-sensitive hypertension identified by expression cloning using the “hot” pepper-derived vanilloid com- pound capsaicin as a ligand. Therefore, TRPV1 is also referred as the vanilloid 1 This work was supported in part by National receptor (VR1) or the capsaicin receptor. VR1 is mainly expressed in a subpopula- Institutes of Health (grants HL-52279 and tion of primary afferent neurons that project to cardiovascular and renal tissues. HL-57853) and a grant from the Michigan These capsaicin-sensitive primary afferent neurons are not only involved in the Economic Development Corporation. 2 Correspondence to Donna H WANG, MD. perception of somatic and visceral pain, but also have a “sensory-effector” function. Phn 1-517-432-0797. Regarding the latter, these neurons release stored neuropeptides through a cal- Fax 1-517-432-1326. cium-dependent mechanism via the binding of capsaicin to VR1. The most studied E-mail [email protected] sensory neuropeptides are calcitonin gene-related peptide (CGRP) and substance Received 2004-08-10 P (SP), which are potent vasodilators and natriuretic/diuretic factors.
    [Show full text]
  • And Substance P and Dumping SEIKI ITO, YOICHI IWASAKI, TAKESHI
    Tohoku J. exp. Med., 1981, 135, 11-21 Neurotensin and Substance P and Dumping Syndrome SEIKI ITO, YOICHI IWASAKI,TAKESHI MOMOTSU, KATSUMI TAKAI,AKIRA SHIBATA, YOICHI MATSUBARA* and TERUKAZU MUTO* The First Department of Internal Medicine and * the First Department of Surgery, Niigata University School of Medicine, Niigata 95.E ITO, S., IWASAKI, Y., MOMOTSU, T., TAKAI, K., SHIBATA, A., MATSUBARA, Y, and MUTO, T. Neurotensin and Substance P and Dumping Syndrome. Tohoku J. exp. Med., 1981, 135 (1), 11-21 To investigste the pathophysiologi- cal relation between releases of gut hormones and dumping syndrome, plasma radioimmunoassayable neurotesin, substance P, glucagon-like immunoreactivity (GLI), insulin and blood sugar were measured in both gastrectomized patients and control subjects after 50 g oral glucose tolerance tests. Remarkable rises of radioimmunoassayable neurotesin and GLI were found in all gastrectomized patients, but not in control subjects. In contrast, plasma radioimmunoassayable substance P responses were not detected in either gastrectomized patients or control subjects. There were three patients with symptoms of dumping syndrome in the early stage of the test. Plasma radioimmunoassayable neurotensin responses in two out of these three were higher than those in other patients, though the other patient with symptoms had the same degree of neurotensin elevation as patients with no symptoms. In view of the pharmacological effects of neurotensin, it could not be ruled out that a part of the early symptoms of dumping syndrome
    [Show full text]
  • Effect of Bradykinin and Eledoisin on Renal Function in the Dog Department of Internal Medicine (Prof. T. Torikai), Tohoku Unive
    Tohoku J. exp. Med., 1966, 89, 69-76 Effect of Bradykinin and Eledoisin on Renal Function in the Dog Takashi Furuyama,. Chikara Suzuki, Hiroshi Saito, Yozo Onozawa , Ryuji Shioji, Shozo Rikimaru, Keishi Abe and Kaoru Yoshinaga Department of Internal Medicine (Prof. T. Torikai), Tohoku University School of Medicine, Sendai Bradykinin (0.05, 0.1 and 0.2 ƒÊg/kg/min) and eledoisin (0.5, 1.0, 5.0 and 10.0ng/kg/min) were infused directly into the left renal artery of anesthetized dogs to demonstrate the effects of these peptides on renal function. Urinary volume, endogenous creatinine clearance (GFR), PAR clearance (RPF) and excretion of electrolytes were increased by infusion of these two peptides, but no constant change was observed in UK/U ,Va ratio. These data demonstrate that the increase in urinary output and electrolyte excretion is caused by the augmentation of tubular load of solutes which resulted from the increase of RPF and GFR. Tachy phylaxis was observed in dogs which received repeated infusions of bradykinin but this phenomenon was less distinct in the case of eledoisin. Bradykinin is a nonapeptide formed by the action of kinin-forming enzymes upon alpha-2-globulin fraction of the plasma and it plays an important role in the local control of blood flow to certain tissues. On the other hand, eledoisin isolated from the salivary gland of Eledone, is endecapeptide having powerful kinin-like activity2. Bradykinin and eledoisin administered intravenously produce reduction in systemic blood pressure because of vasodilator action of the peptides.2,3 Since the change in systemic blood pressure affects renal function in experiments with intravenous infusion of the peptides, it is difficult to reveal their direct action on the kidney.
    [Show full text]
  • Biologically Active Peptides from Australian Amphibians
    Biologically Active Peptides from Australian Amphibians _________________________________ A thesis submitted for the Degree of Doctor of Philosophy by Rebecca Jo Jackway B. Sc. (Biomed.) (Hons.) from the Department of Chemistry, The University of Adelaide August, 2008 Chapter 6 Amphibian Neuropeptides 6.1 Introduction 6.1.1 Amphibian Neuropeptides The identification and characterisation of neuropeptides in amphibians has provided invaluable understanding of not only amphibian ecology and physiology but also of mammalian physiology. In the 1960’s Erspamer demonstrated that a variety of the peptides isolated from amphibian skin secretions were homologous to mammalian neurotransmitters and hormones (reviewed in [10]). Erspamer postulated that every amphibian neuropeptide would have a mammalian counterpart and as a result several were subsequently identified. For example, the discovery of amphibian bombesins lead to their identification in the GI tract and brain of mammals [394]. Neuropeptides form an integral part of an animal’s defence and can assist in regulation of dermal physiology. Neuropeptides can be defined as peptidergic neurotransmitters that are produced by neurons, and can influence the immune response [395], display activities in the CNS and have various other endocrine functions [10]. Generally, neuropeptides exert their biological effects through interactions with G protein-coupled receptors distributed throughout the CNS and periphery and can affect varied activities depending on tissue type. As a result, these peptides have biological significance with possible application to medical sciences. Neuropeptides isolated from amphibians will be discussed in this chapter, with emphasis on the investigation into the biological activity of peptides isolated from several Litoria and Crinia species. Many neurotransmitters and hormones active in the CNS are ubiquitous among all vertebrates, however, active neuropeptides from amphibian skin have limited distributions and are unique to a restricted number of species.
    [Show full text]
  • Wo 2009/015286 A2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 29 January 2009 (29.01.2009) WO 2009/015286 A2 (51) International Patent Classification: Not classified AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY,BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, (21) International Application Number: EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, PCT/US2008/071055 IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY,MA, MD, ME, MG, MK, MN, MW, (22) International Filing Date: 24 July 2008 (24.07.2008) MX, MY,MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TJ, (25) Filing Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 60/961,872 24 July 2007 (24.07.2007) US GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), (71) Applicant (for all designated States except US): NEXBIO, European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, INC. [US/US]; 10665 Sorrento Valley Road, San Diego, California 92121 (US). FR, GB, GR, HR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, (72) Inventors; and CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
    [Show full text]
  • The Hydrolysis of Inositol Phospholipid in Mouse Exocrine Pancreas
    THE HYDROLYSIS OF INOSITOL PHOSPHOLIPID IN IVIOUSE EXOCRINE PANCREAS ,,r'ir:::'r]. *. DEGREE OF DOCTOR OF PHILOSOPHY of The Department of Physiology Uni vers i ty of Adel ai de , South Austra'l i a by KARIN ANNE TENNES B.Sc.(Hons.) 1984 fi.6sx'-eL,'( I ? - S" 8:'" TABLE OF CONTENTS Page SUMMARY . (v.ii) DECLARATI0N (x) AC KNOI,ILEDGEMENTS (xi ) LIST OF TABLES (xii) LIST 0F FIGURES (xiv) CHAPTER 1 : INTRODUCTION 2 CHAPTER 2 LITERATURE REVIEI^, I 2.t PANCRIATIC STRUCTURE AND FUNCTION 9 2.2 INTERACTION BETI^IEEN ENDOCRINE AND EXOCRINE PANCREAS 23 2.3 PANCREATIC SECRETAGOGUES 27 2.3 (a) Secretagogues which Increase the Intra- cel I ul ar Concentrati on of Cal ci um 27 2.3 (b) Secretagogues wh'ich Cause an Increase in the Intracel I ul ar Concentrati on of cAl'lP 28 2.3 (c) Pancreatic Secretagogues which do not Appear to Act via Increas'ing the Intra- cellular Concentration of Calcium or cAMP 42 2.4 THE ROLE OF CALCIUM IN PANCREATIC ENZYIrIE SECRETION 47 2.a G) Evidence for the Involvement of Calcium in Pancreatic Enzyme Secretion 47 2.4 (b) Evidence for the Involvement of Changes i n l,lembrane Potenti al i n Protei n Secreti on 49 2.a (c) Cytop'lasmic Calcium Concentrations in Pancreatic Acinar Cells 56 ( j ) (i i ) Page 2.5 CALCIUM FLUXES IN PANCREATIC ACINAR CELLS : THE EVENTS LEADING TO INCREASID INTRACELLULAR CALCIUM CON CENTRATI ON 60 2.6 THE RELATIONSHIP BETI^IEEN INHIBITION OF PROTEIN SECRETION, CYTOSOLIC CALCIUM CONCENTRATION AND RECEPTOR OCCUPATION IN THE EXOCRINE PANCREAS 70 2.7 CALCIUM-ACTIVATED STIMULUS-SECRETION COUPLING IN EXOCRINE
    [Show full text]
  • JOHN R. VANE Wellcome Research Laboratories, Langley Court, Beckenham, Kent, U.K
    ADVENTURES AND EXCURSIONS IN BIO- ASSAY: THE STEPPING STONES TO PROSTACYCLIN Nobel lecture, 8 December, 1982 by JOHN R. VANE Wellcome Research Laboratories, Langley Court, Beckenham, Kent, U.K. Physiology has spawned many biological sciences, amongst them my own field of pharmacology. No man has made a more important contribution to the fields of physiology and pharmacology than Sir Henry Dale (1875-1968, Nobel Laureate in Physiology or Medicine in 1936). Dale had a great influence not only on British pharmacology in general but also on my own scientific endea- vours. Indeed, I can put forward a strong case for considering myself as one of Dale’s scientific grandchildren. My early days as a pharmacologist were in- fluenced not only by Dale himself but also by his school of colleagues, including Burn, Gaddum and von Euler. It was Burn who taught me the principles and practice of bioassay. Some of Gaddum’s first publications were on the develop- ment of specific and sensitive methods for biological assay and he maintained a deep interest in this subject for the rest of his life (1). In 1964 he said “the pharmacologist has been a ‘jack of all trades’ borrowing from physiology, biochemistry, pathology, microbiology and statistics – but he has developed one technique of his own, and that is the technique of bioassay” (2). Expensive, powerful and sophisticated chemical methods, such as gas chro- matography and mass spectrometry, have been developed and perfected for detection and quantification of prostaglandins (PGs) and related substances. One should not forget, however, that starting with the discovery and isolation of prostaglandins by von Euler (3; see also Bergstrom in this volume), biologi- cal techniques and bioassay have contributed very substantially to the develop- ment of the field.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2015/0050713 A1 Malakhov Et Al
    US 2015.0050713A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0050713 A1 Malakhov et al. (43) Pub. Date: Feb. 19, 2015 (54) TECHNOLOGY FOR THE PREPARATION OF Publication Classification MCROPARTICLES (51) Int. Cl. (71) Applicant: Ansun Biopharma, Inc., San Diego, CA CI2N 9/96 (2006.01) (US) CI2N 7/00 (2006.01) CI2N IS/II3 (2006.01) (72) Inventors: Michael P. Malakhov, San Francisco, C07D 305/.4 (2006.01) CA (US); Fang Fang, Rancho Santa Fe, C07K 4/765 (2006.01) CA (US) C07K9/00 (2006.01) (52) U.S. Cl. CPC ................ CI2N 9/96 (2013.01); C07K 14/765 (21) Appl. No.: 14/341,502 (2013.01); C07K9/008 (2013.01): CI2N 15/113 (2013.01); C07D 305/14 (2013.01); (22) Filed: Jul. 25, 2014 CI2N 7/00 (2013.01); C12N 2770/00051 (2013.01) O O USPC ........... 435/188: 530/363; 530/350, 530/367; Related U.S. Application Data 530/385:536/16.8; 536/13.7: 540/336; 530/317; (63) Continuation of application No. 13/874,424, filed on 536/24.5; 530/328; 552/203; 549/510; 435/238 Apr. 30, 2013, now abandoned, which is a continuation (57) ABSTRACT of application No. 13/250,653, filed on Sep. 30, 2011, Mi h duced b tacti lution of a now abandoned, which is a continuation of application 1crospneres are produced by contacting a sol No. 12/179.520, filed on Jul 24, 2008, now aban- macromolecule or small molecule in a solvent with an ant1 doned sa- 1 ws s s Solvent and a counterion, and chilling the solution.
    [Show full text]
  • Neuropeptides in the Human Brainstem
    Investigación Clínica ISSN: 0535-5133 Universidad del Zulia Duque-Díaz, Ewing; Martínez-Rangel, Diana; Ruiz-Roa, Silvia Neuropeptides in the human brainstem Investigación Clínica, vol. 59, no. 2, 2018, April-June, pp. 161-178 Universidad del Zulia DOI: https://doi.org/10.22209/IC.v59n2a06 Available in: https://www.redalyc.org/articulo.oa?id=372960175007 How to cite Complete issue Scientific Information System Redalyc More information about this article Network of Scientific Journals from Latin America and the Caribbean, Spain and Journal's webpage in redalyc.org Portugal Project academic non-profit, developed under the open access initiative Invest Clin 59(2): 161 - 178, 2018 https//doi.org/10.22209/IC.v59n2a06 Neuropeptides in the human brainstem. Ewing Duque-Díaz1, Diana Martínez-Rangel1 and Silvia Ruiz-Roa1,2. 1Universidad de Santander UDES. Laboratory of Neuroscience, School of Medicine, Bucaramanga, Colombia. 2Universidad de Santander UDES. Laboratory of Neuroscience, Nursing Program, Bucaramanga, Colombia. Key words: neuropeptides; mesencephalon; pons; medulla oblongata; human. Abstract. The physiological importance of the brainstem has made it one of the most studied structures of the central nervous system of mammals (in- cluding human). This structure receives somatic and visceral inputs and its neurons send motor efferences by means of the cranial nerves, which innervate the head, neck and sensory organs, and it mediates in several actions such as movement, pain, cardiovascular, respiratory, salivary, sleep, vigil and sexual mechanisms. Most of these actions are mediated by neuroactive substances denominated neuropeptides, which are short amino acid chains widespread dis- tributed in the nervous system, that play a role in neurotransmission, neuro- modulation (paracrine and autocrine actions), and act as neurohormones.
    [Show full text]