DOCSLIB.ORG

Fifty Years of Substance P P Itself

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Fifty Years of Substance P P Itself Nature Vol. 295 18 February 1982 551 responses that resembles, but greatly outlasts, the response elicited by substance Fifty years of substance P P itself. The prolonged duration of action from T.M. Jessel/ of Di Me C7 in vivo provides the first indication that substance P-inactivating SUBSTANCE P, the doyen of the common agonists and analogues that are selective enzymes may in fact function physio­ peptides 1, is now 50 years old and on the for substance P receptor subtypes within logically. verge of achieving respectability as a neuro­ the central (CNS) and peripheral nervous Comparison of the potency of substance transmitter. Yet by comparison with many systems (see Table 1). By substituting P and its analogues on a battery of other peptides of inferior pedigree, the d-amino acids at residues 7 and 9, Rosell different bioassay systems is beginning to physiological functions of substance P (Karolinska Institute) and colleagues have generate a pattern of activity which may have remained obscure. Some of the synthesized a peptide analogue that reflect the existence of at least two reasons for the slow progress are easy to antagonizes the spasmogenic activity of subclasses of substance P receptors. The find. Although many of the peripheral substance P on intestinal smooth muscle clearest demonstration of this derives from actions and chemical properties were estab­ and the vasodilatory actions on peripheral studies with the tachykinins, a family of lished byvon Euler and Gaddum, it took40 vessels. At present, effective blockade of naturally occurring peptides isolated from years before substance P was eventually substance P responses can be achieved only amphibian skin, which share a common isolated and its amino acid sequence at relatively high antagonist concentrations C-terminal amino acid sequence with sub­ 5 determined. But even with the availability (10· -I0-4M) and partial agonist activity stance P 4 • For example, substance Pis five of synthetic material, advances in the has also been observed in some bioassav times more potent than the tachykinin chemistry of substance P have been disap­ systems2 • However, more potent ana kassinin as a spasmogen in the guinea pig pointingly slow. Simple modifications in specific antagonists can now be anticipated ileum, but is 100-1,000 times less active the native amino acid sequence did not im­ and their availability will undoubtedly than kassinin in potentiating the electri­ mediately generate receptor antagonists or prove crucial for evaluating many of the cally evoked contraction of the rat vas more potent agonists. More fundamental postulated physiological functions of sub­ deferens. Iversen and Hanley (MRC perhaps, the behaviour elicited by the stance P. Neurochemical Pharmacology Unit) have central or peripheral application of Attaching a methyl group to the nitrogen now extended this analysis to synthetic substance P has been less easily inter­ atom in the peptide bonds at residues 8 and substance P analogues, including the pretable than, for example, the elevation of 9 and deleting the N-terminal tetrapeptide methyl ester of substance P, which is pain threshold associated with adminis­ (Lee, Johns Hopkins Medical School) 10,000 times less active than kassinin on the tration of opioid peptides or the modi­ results in an analogue (termed Di Me C7) rat vas deferens but equipotent on the fication of feeding and drinking behaviour which is biologically active and completely guinea pig ileum5 • Iversen and Hanley have elicited by cholecystokinin and resistant to degradation by a membrane­ consequently introduced the terminology angiotensin. bound endopeptidase that inactivates SP-P and SP-E receptors to represent these At a recent CIBA Foundation substance P 3 • Whether the endopeptidase two extremes of biological activity. SP-P symposium* there were encouraging signs isolated by Lee, or any other enzyme for receptors predominate in the guinea pig that some of these obstacles have been, or which substance P can act as a substrate, is ileum and exhibit greatest selectivity for the are about to be, overcome. In particular, it actually involved in the inactivation of methyl ester of substance P and the tachy­ is now apparent that modifications of the neuronally released substance P is still kinin physalaemin. SP-E receptors are C-terminal sequence of substance P can unclear. It is conceivable that diffusion present in the rat vas deferens and are generate receptor antagonists, stable alone could effectively terminate the activated most potently by the tachykinins •CIBA Foundation Symposium no.91 'Substance P in the actions of substance P. However, injection eledoisin and kassinin. Synthetic substance Nervous System', organized by Dr Ruth Porter and chaired by Sir Arnold Burgen. was held at the CIBA Foundation 30 of Di Me C7 into the ventral tegmental area P analogues exhibiting specificity for CNS November - 3 December 1981 and followed by a one day of rats (Iversen, University of Cambridge) meeting organized by the Centre for Neuroscience at University receptors may also exist. Iversen reported College London. produces a spectrum of behavioural that extension of the C-terminal amide group produces an analogue that is ten seems probable that if a venomous snake's times more potent than substance P itself in fangs lay in its tail, it would use its teeth first displacing 3H-labelled substance P binding when attacked before bringing them into play. to rat brain membranes but has I was walking in the Botanical Gardens of only one­ Rio de Janeiro some time ago, when I found thousandth its potency on peripheral bio­ myself literally upon an immense green tree­ assay systems (Table 1). snake, at least nine or ten feet long. This The existence of mammalian receptor serpent, of course, was harmless, so that there subtypes that exhibit selectivity for 100 years ago would have been no danger in grasping it; but peptides of amphibian or arthropod origin it emitted a curious sound in its terror, such as raises the possibility NOTES ABOUT SNAKES that similar tachy­ I have never heard before or since. It kinins may also exist in mammalian A serpent's first instinctive impulse of self­ screamed, and so loudly, that some people species. In fact, Lazarus et al. have recently preservation, like that of every other animal, near, who saw nothing of what was going on, reported low lies in escape; probably a more nervous thought they heard a child cry. Serpants make amounts of physalaemin-like 6 creature does not exist. If surprised suddenly, all sorts of noises besides hissing, according to peptide in rat brain and intestine • In or brought to bay at close quarters, it may be their different kinds; Crotali spring their addition, Keen (University of Bristol) has too terror-stricken to attempt flight; then it rattles; the carpet-viper (Echis carinata) rubs observed that rat dorsal root ganglia bites, following a curious general rule which the imbricated scales of its adjacent coils incubated with 35 S-methionine can syn­ seems to obtain throughout nearly the whole together; the fer-de-lance (Trigonocephalus thesize authentic substance P and also a animal world, from a passionate child down­ /anceolatus) is said in St. Lucia to give out a peptide that is immunoprecipitated by ward, no matter what the natural weapons of series of little taps with its horny extremity; C-terminal- but not N-terminal-specific offence may be. Young Felidoe will keep their and many others - such as the rat-snake anti-substance 7 • talons sheathed until they have exterted P antisera Although the all (Spilotes variabilis) of South America - cer­ identity possible force with their soft milk-teeth, and a of this peptide is unknown, these tainly indicate their presence when angry by findings suggest that there may be a second lizard will seize the hand which restrains it with quivering their tails against the ground; but a its insignificant little jaws, when its tail or crying snake would have been a decided claws might inflict far more injury. The novelty in one's collection. Boidoe never use their constrictive powers in ARTHUR STRADLING T.M. Jessel/ is in the Department of Neuro­ self-defence (unless they arc gripped), and it From Nature 25, 16 February, 377, 1882. biology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115. 0028-0836/ 82/ 07055 I 03 SOl.00 @ 1982 Macmillan Journals Lid .
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]
  • V·M·I University Microfilms International a Bell & Howell Information Company 300 North Zeeb Road, Ann Arbor
    Characterization of the cloned neurokinin A receptor transfected in murine fibroblasts Item Type text; Dissertation-Reproduction (electronic) Authors Henderson, Alden Keith. Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 27/09/2021 18:29:56 Link to Item http://hdl.handle.net/10150/185828 1/. INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note. will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy.
    [Show full text]
  • Identification of a Novel Vasodilatory Octapeptide from the Skin Secretion
    molecules Article Identification of a Novel Vasodilatory Octapeptide from the Skin Secretion of the African Hyperoliid Frog, Kassina senegalensis Qiang Du 1,†, Hui Wang 1,*,†, Chengbang Ma 2, Yue Wu 2, Xinping Xi 2,*, Mei Zhou 2 ID , Tianbao Chen 2 ID , Chris Shaw 2 and Lei Wang 2 1 School of Pharmacy, China Medical University, Shenyang 110001, Liaoning, China; [email protected] 2 Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK; [email protected] (C.M.); [email protected] (Y.W.); [email protected] (M.Z.); [email protected] (T.C.); [email protected] (C.S.); [email protected] (L.W.) * Correspondence: [email protected] (H.W.); [email protected] (X.X.); Tel.: +86-24-2325-6666 (H.W.); +44-28-9097-2200 (X.X.); Fax: +86-2325-5471 (H.W.); +44-28-9094-7794 (X.X.) † These authors contributed equally to this work. Received: 5 July 2017; Accepted: 19 July 2017; Published: 19 July 2017 Abstract: The defensive skin secretions of amphibians continue to be an excellent source of novel biologically-active peptides. Here we report the identification and pharmacological activity of a novel C-terminally amided myotropic octapeptide from the skin secretion of the African hyperoliid frog, Kassina senegalensis. The 8-amino acid peptide has the following primary structure: WMSLGWSL-amide and has a molecular mass of 978 Da. The primary structure and organisation of the biosynthetic precursor of WL-8 amide was successfully deduced from cloned skin secretion-derived cDNA.
    [Show full text]
  • Peptide Chemistry up to Its Present State
    Appendix In this Appendix biographical sketches are compiled of many scientists who have made notable contributions to the development of peptide chemistry up to its present state. We have tried to consider names mainly connected with important events during the earlier periods of peptide history, but could not include all authors mentioned in the text of this book. This is particularly true for the more recent decades when the number of peptide chemists and biologists increased to such an extent that their enumeration would have gone beyond the scope of this Appendix. 250 Appendix Plate 8. Emil Abderhalden (1877-1950), Photo Plate 9. S. Akabori Leopoldina, Halle J Plate 10. Ernst Bayer Plate 11. Karel Blaha (1926-1988) Appendix 251 Plate 12. Max Brenner Plate 13. Hans Brockmann (1903-1988) Plate 14. Victor Bruckner (1900- 1980) Plate 15. Pehr V. Edman (1916- 1977) 252 Appendix Plate 16. Lyman C. Craig (1906-1974) Plate 17. Vittorio Erspamer Plate 18. Joseph S. Fruton, Biochemist and Historian Appendix 253 Plate 19. Rolf Geiger (1923-1988) Plate 20. Wolfgang Konig Plate 21. Dorothy Hodgkins Plate. 22. Franz Hofmeister (1850-1922), (Fischer, biograph. Lexikon) 254 Appendix Plate 23. The picture shows the late Professor 1.E. Jorpes (r.j and Professor V. Mutt during their favorite pastime in the archipelago on the Baltic near Stockholm Plate 24. Ephraim Katchalski (Katzir) Plate 25. Abraham Patchornik Appendix 255 Plate 26. P.G. Katsoyannis Plate 27. George W. Kenner (1922-1978) Plate 28. Edger Lederer (1908- 1988) Plate 29. Hennann Leuchs (1879-1945) 256 Appendix Plate 30. Choh Hao Li (1913-1987) Plate 31.
    [Show full text]
  • Neuropeptide Proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH)
    Proc. NatL Acad. Sci. USA Vol. 78, No. 9, pp. 5899-5902, September 1981 Neurobiology Neuropeptide proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH): Immunological detection and neuronal localization in insect central nervous system (peptide neurotransmitter/identified neurons) CYNTHIA A. BISHOP, MICHAEL O'SHEA*, AND RICHARD J. MILLER The Department of Pharmacological and Physiological Sciences, The University of Chicago, 947 E. 58th Street, Chicago, Illinois 60637 Communicated by Solomon H. Snyder, June 19, 1981 ABSTRACT Proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH) is a pen- vestigation ofneuropeptide action in a relatively simple nervous tapeptide first extracted from cockroaches. It is known to have system. many neurohormonal effects and has been associated with spe- cific, identified cockroach neurons. We have produced proctolin MATERIALS AND METHODS antisera and report here on their application in detecting proc- tolin-like immunoreactivity (PLI) in the cockroach central nervous Adult specimens, both male and female, of the large American system. Radioimmunoassay, capable ofdetecting 50 fmol ofproc- cockroach (Periplaneta americana; Carolina Biological Supply, tolin, was used to quantify the distribution of PLI. Highest con- Burlington, NC) were used. Authentic proctolin for immuni- centrations were detected in the genital ganglia and lowest in the zation was obtained from Sigma. Enkephalins were.a gift of S. cerebral ganglia. Immunohistochemistry on the cockroach central Wilkinson, Wellcome Research Laboratories (Beckenham, nervous system demonstrated that PLI is localized to neurons. Kent, England). Gut bombesin was a gift of J. Rivier, Salk In- Neurons stained by using immunohistochemistry were widespread stitute (La Jolla, CA). Other peptides were obtained from in the ganglia.
    [Show full text]
  • A 0.70% E 0.80% Is 0.90%
    US 20080317666A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0317666 A1 Fattal et al. (43) Pub. Date: Dec. 25, 2008 (54) COLONIC DELIVERY OF ACTIVE AGENTS Publication Classification (51) Int. Cl. (76) Inventors: Elias Fattal, Paris (FR); Antoine A6IR 9/00 (2006.01) Andremont, Malakoff (FR); A61R 49/00 (2006.01) Patrick Couvreur, A6II 5L/12 (2006.01) Villebon-sur-Yvette (FR); Sandrine A6IPI/00 (2006.01) Bourgeois, Lyon (FR) (52) U.S. Cl. .......................... 424/1.11; 424/423; 424/9.1 (57) ABSTRACT Correspondence Address: Drug delivery devices that are orally administered, and that David S. Bradlin release active ingredients in the colon, are disclosed. In one Womble Carlyle Sandridge & Rice embodiment, the active ingredients are those that inactivate P.O.BOX 7037 antibiotics, such as macrollides, quinolones and beta-lactam Atlanta, GA 30359-0037 (US) containing antibiotics. One example of a Suitable active agent is an enzyme Such as beta-lactamases. In another embodi ment, the active agents are those that specifically treat colonic (21) Appl. No.: 11/628,832 disorders, such as Chrohn's Disease, irritable bowel syn drome, ulcerative colitis, colorectal cancer or constipation. (22) PCT Filed: Feb. 9, 2006 The drug delivery devices are in the form of beads of pectin, crosslinked with calcium and reticulated with polyethylene imine. The high crosslink density of the polyethyleneimine is (86). PCT No.: PCT/GBO6/OO448 believed to stabilize the pectin beads for a sufficient amount of time such that a Substantial amount of the active ingredi S371 (c)(1), ents can be administered directly to the colon.
    [Show full text]
  • 251-Bolton-Hunter- Labeled Substance P Binding Sites in Rat Spinal Cord’
    0270.6474/65/0505-1293$02.00/O The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 5, No. 5, pp. 1293-1299 Printed in U.S.A. May 1985 Characterization and Segmental Distribution of ‘251-Bolton-Hunter- labeled Substance P Binding Sites in Rat Spinal Cord’ CLIVEL G. CHARLTON’ AND CINDA J. HELKE Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814 Abstract al., 1982) are two sources for SP in the ventral horn. The nucleus interfascicularis hypoglossi also supplies SP-containing nerve termi- Substance P (SP) is widely distributed in the spinal cord nals to the IML cells of origin for autonomic preganglion fibers (Helke and has been implicated as a neurotransmitter in several et al., 1982). spinal cord neuronal systems. To investigate SP receptors in Functional studies support the concept of a neurotransmOitter role the spinal cord, 1251-Bolton-Hunter-SP (‘*‘I-BH-SP) was used for SP in the spinal cord. Nociception (Piercey et al., 1981; Akerman to identify and characterize spinal cord binding sites for the et al., 1982; Fasmer and Post, 1983) motor control (Otsuka and peptide. The binding of ‘*%BH-SP had the following charac- Konishi, 1977; Yanagisawa et al., 1982) and certain autonomic teristics: high affinity; time, temperature, and membrane con- functions (Loewy and Sawyer, 1982; Keeler and Helke, 1984) are centration dependent; reversible; and saturable. The KS0 of modulated by spinal cord SP. In addition, SP receptors in the spinal SP in whole spinal cord was 0.46 nM as compared with 0.95, cord have been demonstrated by iontophoretic studies in which SP 60, and 150 nM for physalaemin, eledoisin, and kassinin.
    [Show full text]
  • The Significance of NK1 Receptor Ligands and Their Application In
    pharmaceutics Review The Significance of NK1 Receptor Ligands and Their Application in Targeted Radionuclide Tumour Therapy Agnieszka Majkowska-Pilip * , Paweł Krzysztof Halik and Ewa Gniazdowska Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland * Correspondence: [email protected]; Tel.: +48-22-504-10-11 Received: 7 June 2019; Accepted: 16 August 2019; Published: 1 September 2019 Abstract: To date, our understanding of the Substance P (SP) and neurokinin 1 receptor (NK1R) system shows intricate relations between human physiology and disease occurrence or progression. Within the oncological field, overexpression of NK1R and this SP/NK1R system have been implicated in cancer cell progression and poor overall prognosis. This review focuses on providing an update on the current state of knowledge around the wide spectrum of NK1R ligands and applications of radioligands as radiopharmaceuticals. In this review, data concerning both the chemical and biological aspects of peptide and nonpeptide ligands as agonists or antagonists in classical and nuclear medicine, are presented and discussed. However, the research presented here is primarily focused on NK1R nonpeptide antagonistic ligands and the potential application of SP/NK1R system in targeted radionuclide tumour therapy. Keywords: neurokinin 1 receptor; Substance P; SP analogues; NK1R antagonists; targeted therapy; radioligands; tumour therapy; PET imaging 1. Introduction Neurokinin 1 receptor (NK1R), also known as tachykinin receptor 1 (TACR1), belongs to the tachykinin receptor subfamily of G protein-coupled receptors (GPCRs), also called seven-transmembrane domain receptors (Figure1)[ 1–3]. The human NK1 receptor structure [4] is available in Protein Data Bank (6E59).
    [Show full text]
  • Targeting the Vasopressin Type 2 Receptor for Renal Cell Carcinoma Therapy
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Oncogene Manuscript Author . Author manuscript; Manuscript Author available in PMC 2020 April 15. Published in final edited form as: Oncogene. 2020 February ; 39(6): 1231–1245. doi:10.1038/s41388-019-1059-0. Targeting the Vasopressin Type 2 Receptor for Renal Cell Carcinoma Therapy Sonali Sinhaa,b, Nidhi Dwivedia,b, Shixin Taoa,b, Abeda Jamadara,b, Vijayakumar R Kakadea,b, Maura O’Neilc, Robert H Weissd,e, Jonathan Endersf, James P Calveta,h,i, Sufi M Thomasg,i, Reena Raoa,b,i aThe Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City,KS. bDepartment of Internal Medicine, University of Kansas Medical Center, Kansas City, KS. cDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS. dDivision of Nephrology and Comprehensive Cancer Center, University of California, Davis, CA. eMedical Service, VA Northern California Health Care System, Sacramento, CA. fDepartment of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS. gDepartment of Otolaryngology, University of Kansas Medical Center, Kansas City, KS. hDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS. iDepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, KS. Abstract Arginine vasopressin (AVP) and its type-2 receptor (V2R) play an essential role in the regulation of salt and water homeostasis by the kidneys. V2R activation also stimulates proliferation of renal cell carcinoma (RCC) cell lines in vitro. The current studies investigated V2R expression and activity in human RCC tumors, and its role in RCC tumor growth.
    [Show full text]
  • Topography of a Binding Site for Small Amnestic Peptides Deduced from Structure-Activity Studies: Relation to Amnestic Effect of Amyloid F8 Protein JAMES F
    Proc. Natl. Acad. Sci. USA Vol. 91, pp. 380-384, January 1994 Neurobiology Topography of a binding site for small amnestic peptides deduced from structure-activity studies: Relation to amnestic effect of amyloid f8 protein JAMES F. FLOOD*, EUGENE ROBERTStt, MARK A. SHERMAN§, BRUCE E. KAPLAN§, AND JOHN E. MORLEY* Geriatric Research Education and Clinical Center (GRECC), Veterans Administration Medical Center, St. Louis, MO 63106, and St. Louis University School of Medicine, Division of Geriatric Medicine, St. Louis, MO 63104; and tDepartment of Neurobiochemistry and §Biology Division, Beckman Research Institute of the City of Hope, Duarte, CA 91010 Contributed by Eugene Roberts, September 7, 1993 ABSTRACT Four peptides homologous to amyloid (B pro- With the exception of commercially purchased peptides tein containng the Val-Phe-Phe (VFF) sequence administered VF and FV, all peptides used in these studies were synthe- intracerebroventricularly after training caused amnesia for sized and analyzed to establish purity by standard methods. footshock active avoidance training in mice. Results with VFF Prior to neutralization and appropriate dilution with saline, and other peptides containing VFF or portions thereof were peptides were dissolved in (i) saline, (ii) dimethyl sulfoxide, used to generate a topographic map for a hypothetical binding (iii) glacial acetic acid, or (iv) NaOH. Upon testing for surface for amnestic peptides, termed Z. Effects on retention of retention of FAAT, groups receiving posttraining icv admin- footshock active avoidance training were rationalized in terms istration of2 1d ofappropriate dilutions ofthe above vehicles of flt to Z, making possible design of potential memory- showed no significant differences among them (ANOVA, F modulating peptidic and nonpeptidic substances.
    [Show full text]
  • Occurrence of Bombesin and Alytesin in Extracts of the Skin of Three
    Br. J. Pharmac. (1972), 45, 333-348. Occurrence of bombesin and alytesin in extracts of the skin of three European discoglossid frogs and pharmacological actions of bombesin on extravascular smooth muscle V. ERSPAMER, G. FALCONIERI ERSPAMER, M. INSELVINI AND L. NEGRI Institute of Medical Pharmacology I, University of Rome, Rome, Italy Summary 1. Methanol extracts of the skin of Bombina bombina and Bombina variegata variegata, two European discoglossid frogs, contain an active tetradecapeptide, bombesin. Alytesin, a tetradecapeptide strictly related to bombesin is present in extracts of the skin of Alytes obstetricans, another European discoglossid frog. The American frog Rana pipiens, contains in its skin ranatensin, an endecapeptide related to bombesin and alytesin. 2. Passage of crude skin extracts of Bombina through a column of alumina yields eluates which may be considered free of other peptide contaminants and are suitable for the isolation of bombesin in a pure form. 3. Bombesin has a stimulant action on several preparations of intestinal, uterine and urinary tract smooth muscle. Sometimes the effect is easily repeatable and shows a fair proportionality to the dose, but at other times a prompt and intense tachyphylaxis is observed. Other smooth muscle prepara- tions are poorly sensitive or insensitive to bombesin. The rat uterus, the kitten small intestine, the guinea-pig colon and the rat urinary bladder may be used for the quantitative bioassay of bombesin. 4. Bombesin-like peptides may easily be distinguished from all other naturally occurring peptides by parallel assay. They constitute a new group of active peptides possessing a peculiar spectrum of activity. Introduction Methanol extracts of the skin of the two European discoglossid frogs Bombina bombina and Bombina variegata variegata contain a principle which displays a number of pharmacological actions on vascular and extravascular smooth muscle and on gastric secretion (Erspamer, Falconieri Erspamer & Inselvini, 1970; Melchiorri, Sopranzi & Erspamer, 1971).
    [Show full text]
  • Tachykinins in Endocrine Tumors and the Carcinoid Syndrome
    European Journal of Endocrinology (2008) 159 275–282 ISSN 0804-4643 CLINICAL STUDY Tachykinins in endocrine tumors and the carcinoid syndrome Janet L Cunningham1, Eva T Janson1, Smriti Agarwal1, Lars Grimelius2 and Mats Stridsberg1 Departments of 1Medical Sciences and 2Genetics and Pathology, University Hospital, SE 751 85 Uppsala, Sweden (Correspondence should be addressed to J Cunningham who is now at Section of Endocrine Oncology, Department of Medical Sciences, Lab 14, Research Department 2, Uppsala University Hospital, Uppsala University, SE 751 85 Uppsala, Sweden; Email: [email protected]) Abstract Objective: A new antibody, active against the common tachykinin (TK) C-terminal, was used to study TK expression in patients with endocrine tumors and a possible association between plasma-TK levels and symptoms of diarrhea and flush in patients with metastasizing ileocecal serotonin-producing carcinoid tumors (MSPCs). Method: TK, serotonin and chromogranin A (CgA) immunoreactivity (IR) was studied by immunohistochemistry in tissue samples from 33 midgut carcinoids and 72 other endocrine tumors. Circulating TK (P-TK) and urinary-5 hydroxyindoleacetic acid (U-5HIAA) concentrations were measured in 42 patients with MSPCs before treatment and related to symptoms in patients with the carcinoid syndrome. Circulating CgA concentrations were also measured in 39 out of the 42 patients. Results: All MSPCs displayed serotonin and strong TK expression. TK-IR was also seen in all serotonin- producing lung and appendix carcinoids. None of the other tumors examined contained TK-IR cells. Concentrations of P-TK, P-CgA, and U-5HIAA were elevated in patients experiencing daily episodes of either flush or diarrhea, when compared with patients experiencing occasional or none of these symptoms.
    [Show full text]