DOCSLIB.ORG

Secretin/Vasoactive Intestinal Peptide-Stimulated Secretion of Bombesin/ Gastrin Releasing Peptide from Human Small Cell Carcinoma of the Lung1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Secretin/Vasoactive Intestinal Peptide-Stimulated Secretion of Bombesin/ Gastrin Releasing Peptide from Human Small Cell Carcinoma of the Lung1 ICANCER RESEARCH 46, 1214-1218, March 1986] Secretin/Vasoactive Intestinal Peptide-stimulated Secretion of Bombesin/ Gastrin Releasing Peptide from Human Small Cell Carcinoma of the Lung1 Louis Y. Korman,2 Desmond N. Carney, Marc L. Citron, and Terry W. Moody Medica/ Service (151W), Veterans Administration Medical Center, Washington, DC 20422 [L. Y.K., M.L.C.]; Department of Medicine and Biochemistry George Washington University School of Medicine, Washington, DC 20037 [T. W. M.¡;and National Cancer Institute-Navy Medical Oncology Branch National Cancer Institute and National Naval Medical Center, Bethesda, Maryland [D. N. C.¡ ABSTRACT autocrine factor for SCCL (12) growth. We studied the mecha nism of BLI secretion in several SCCL cell lines by examining Bombesin/gastrin releasing peptide-like immunoreactivity (BLI) the action of agents that increase intracellular cAMP. is found in the majority of small cell carcinoma of the lung (SCCL) Because of the results of these in vitro studies and the fact cell lines examined. Because BLI is present in high concentration that secretin stimulates hormone release in patients with gastrin in SCCL we studied the mechanism of BLI secretion from several producing tumors (Zollinger-Ellison syndrome), we examined the SCCL cell lines and in patients with SCCL. In cell line NCI-H345 action of i.v. secretin infusion on plasma BLI levels in several the structurally related polypeptide hormones secretin, vasoac- patients with SCCL, non-SCCL lung tumors, and patients with tive intestinal peptide, and peptide histidine isoleucine as well as theophylline, a phosphodiesterase inhibitor, N6,O2'-dibutyryl out any cancer. cyclic adenosine 3':5'-monophosphate, a cyclic nucleotide ana logue, increased BLI release by 16-120% and cyclic adenosine MATERIALS AND METHODS 3':5'-monophosphate by 36-350%. Similar results were ob Cell Culture. SCCL cell line NCI-H345 was established using a bone tained in SCCL cell line NCI-H209. i.v. injection of secretin (2 biopsy from a patient with SCCL who had relapsed following intensive units/kg) significantly increased plasma BLI in 2 patients with combination chemotherapy. In culture NCI-H345 is aneuploid, clonogenic extrapulmonary SCCL. These data suggest that SCCL cells in soft agarose, tumorigenic in nude mice, expresses elevated levels of 3,4-dihydroxy-L-phenylalanine decarboxylase (198 units/mg protein), possess receptors for secretin/vasoactive intestinal peptide and that receptor occupation stimulates in vitro and In vivo BLI neuron specific enolase (4075 ng/mg protein), and produces high quan tities of BLI (4.7 pmol/mg protein (2). The cell line was maintained secretion. continuously for 24 mo in a serum free defined HITES medium (13). Cells were incubated in 75-cm2 Falcon tissue culture flasks in a humidified INTRODUCTION atmosphere of 5% CO2/95% air at 37°C. One to 2 wk prior to each experiment stock cultures were passaged and then 3 days prior to use In the United States, small cell carcinoma of the lung accounts the cells were resuspended in fresh HITES medium. Other SCCL cell for 25,000-30,000 new cases of primary lung cancer each year lines were maintained as described previously (2). (1). Unlike the other major forms of lung cancer, in vivo and in BLI Radioimmunoassay. Rabbit antisera to bombesin was obtained vitro studies indicate that SCCL3 expresses several unique cy- as described previously (14). The antiserum recognizes bombesin and the structurally related gastrin releasing peptide equally well, because tochemical and functional characteristics including the presence they have the same COOH-terminal heptapeptide, and does not cross- of high levels of 3,4-dihydroxy-L-phenylalanine decarboxylase, react with secretin, VIP, or PHI (14). For the BLI determination cells or dense core neurosecretory granules, and the secretion of peptide supernatant was extracted with boiling 2 N acetic acid, centrifuged at hormones (2-4). These findings suggest that SCCL may origi 2,000 x g for 10 min to remove paniculate material, and the supernatant nate from endocrine (Kultschitzky) cells in the lung (5). However, was frozen, lyophilized, and stored at -70°C. The assay was performed recent studies indicate that SCCL may be derived from a he- by resuspending samples in 140 mw NaCI/16 mw NaPO4 (pH 7.4) matopoietic stem cell (6). Although several polypeptide hor containing 0.25% bovine serum albumin and incubating with rabbit anti- mones including adrenocorticotropic hormone, calcitonin, phys- bombesin serum at 1:100,000 dilution for 1 h at 4°C,then adding 5000 cpm of 125l-labeled tyrosine4 bombesin for a total vol of 400 pi and alaemin, arginine vasopressin, and neurotensin are produced by incubated for 16 h at 4°C.At the end of the incubation 200 pi of normal SCCL, BLI is frequently present (4, 7-9). Prior investigations rabbit serum at 1:200 dilution was added followed by 100 pi of goat anti- have demonstrated that hormone secretion from cultured endo rabbit serum at 1:20 dilution. After 30 min, 200 pi of 12% polyethylene crine cells including SCCL (10) may be mediated by the intracel- glycol was added to enhance precipitation and the samples were centri lular second messenger cAMP (11) and bombesin may be an fuged at 1000 x g for 20 min. The supernatant was removed and the pellet assayed for antibody-tracer complex in a LKB gamma counter Received 2/18/85; revised 7/30/85, 11/26/8S; accepted 12/2/85. 1This work was supported by funds from the Veterans Administration Research (LKB, Rockville, MD). Service and by National Cancer Institute grant CA-33767. Presented in part at the Venous blood samples were centrifuged in a Sorvall RC-5B refriger Annual Meeting of the American Federation for Clinical Research, Washington DC ated centrifuge at 500 x g for 10 min and the plasma was removed and April 1983. stored at -70°C. Prior to assay the plasma was thawed and processed 2 To whom requests for reprints should be addressed, at Gastroenterology Section (151 W), Veterans Administration Medical Center, 50 Irving St., NW, Wash using a modification of the method of Bohlen ef a/. (15). In brief, 2 ml of ington, DC 20422. plasma were added to 6 ml of 5% formic acid, 15% trifluoracetic acid, 3 The abbreviations used are: SCCL, small cell carcinoma of the lung; BLI, 9% HCI, and 1% NaCI. The precipitated plasma proteins were centrifuged bombesin/gastrin releasing peptide-like immunoreactivity; cAMP, cyclic AMP; VIP, at 2000 x g for 10 min and the supernatant was applied to a Sep-Pak vasoactive intestinal peptide; PHI, peptide histidine isoleucine; HITES (medium), RPMI 1640 medium supplemented with hydrocortisone (10 nM), bovine insulin (5 (Millipore). The peptides were eluted from the Sep-Pak using ethanol/0.2 fig/ml), transferrin (10 jig/ml), 17^-estradiol (10 nw), and sodium selenite (30 nM)- N HCI (1/1), and the eluate was frozen, lyophilized, and assayed for BLI cGMP, cyclic GMP. (14). CANCER RESEARCH VOL. 46 MARCH 1986 1214 Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 1986 American Association for Cancer Research. BOMBESIN/GASTRIN RELEASING PEPTIDE SECRETION FROM HUMAN SCCL Cyclic AMP Radioimmunoassay. Cyclic AMP was determined using mg protein by 5 min which declined to 39 pmol/mg protein by a minor modification (16) of the procedure described by Brooker ef al. 60 min. Similarly, 1 I¿Msecretin, a gastrointestinal peptide with (17). At the times specified iced (4°C)absolute ethanol was added to an equal vol of either the cell suspension or the cell pellet, kept at 4°Cfor significant sequence homology to VIP (20), increased cAMP from 15 min and then frozen and stored at -70°C. Samples were thawed and 17 to 42 pmol/mg protein by 60 min. Without additions cAMP varied between 10 and 25 pmol/mg protein during the 60-min centrifuged at 10,000 x g for 5 min, and an aliquot of supernatant was incubation. Equivalent results were obtained for cell line NCI- removed and assayed for cAMP. Protein was measured by the method described by Lowry ef at. (18). H209 (data not shown). Secretin Infusion. Secretin (2 units/kg) was injected over a 30-s Fig. 2 shows that 1 »Msecretin increased BLI in the superna period into a large antecubital vein via a freely flowing i.v. At 15 min, just tant from 300 to 480 fmol/mg protein after 5 min. Secretion then prior to and at 2, 5,10, 30, and 60 min after secretin injection 5-ml blood remained constant in the presence of 1 /IM secretin. In contrast, samples were obtained, added to 0.5 ml of 20 HIM ethyleneglycol bis(/3- without additions supernatant BLI remained constant at 250 aminoethyl ether)-A/,A/,/v",A/'-tetraacetic acid and bacitracin (pH 7.4), 1 fmol/mg protein throughout the time course of the experiment. mg/ml and placed on ice. Symptoms, blood pressure, pulse, and respi These data indicate that 1 /.M secretin stimulated a rapid release ratory rate were monitored during and for 2 h after secretin injection and of BLI into the supernatant and this release coincided with the no untoward effects occurred. Informed consent, approved by the Med secretin-stimulated increase in cAMP. Similar results were ob ical Center Human Studies Subcommittee, was obtained from the pa tained using VIP. Because both the cAMP levels and secretion tients. Materials. RPM11640 with glutamine was obtained from Grand Island of BLI was maximal after 5 min this time point was used in all Biological, Grand Island, NY; VIP, PHI, secretin, bombesin, physalaemin, subsequent in vitro experiments. Table 1 shows that at 5 min, neurotensin, and cholecystokinin-octapeptide from Peninsula Laborato when secretagogue-stimulated cAMP was maximal, 1 ^M VIP, ries, Belmont, CA; bovine plasma albumin (Fraction V) from Armour PHI, or secretin significantly (21) increased BLI release by 25, Pharmaceutical, Phoenix, AZ; all other chemicals were from Sigma Chemical, St.
Load more

Recommended publications
  • Fast Cancer Uptake of 99Mtc-Labelled Bombesin (99Mtc BN1)
    in vivo 19: 1071-1076 (2005) Fast Cancer Uptake of 99mTc-labelled Bombesin (99mTc BN1) F. SCOPINARO1, G. P. DI SANTO1, A. TOFANI1, R. MASSARI2, C. TROTTA2, M. RAGONE3, S. ARCHIMANDRITIS4 and A.D. VARVARIGOU5 1Department of Scienze Radiologiche and 4Faculty of Engineering, University “La Sapienza”, Rome; 2University Hospital “San Andrea”, Rome; 3Li-Tech and ISIB-CNR, Udine and Rome, Italy; 5National Research Center,"Demokritos", Athens, Greece Abstract. In human blood, breakdown of gastrin-releasing show istant action because BN receptors (BNRs) and BNR peptide and other bombesin-related peptides occurs in less than subtypes (BNS) are the same in different tissues; however, 15 min. This quick enzymatic cleavage might impair the the action of the above peptides is prevented by their rapid diagnostic use of labelled bombesin (BN). 99mTc-labelled breakdown in the serum. bombesin (99mTc BN1) was injected intravenously and BN and BN-related peptides are neuro-hormones and dynamic uptake data were acquired for diagnosing 26 cancers neurotransmitters; the three well known human BNS show a of different origin: 15 breast, 3 prostate, 5 colo-rectal, 1 number of functions in the central nervous system (4, 5). pancreas, 2 small cell lung cancers and 1 gastrinoma. BNS is also expressed in several foetal and adult tissues, Background subtracted tumour uptake data were plotted where BN-related peptides act as releasing factors, against time and fitted with known mathematical functions. morphogens and growth factors (6-8). Finally, BN-related Twenty-three out of 26 cancers showed rapid increase of peptides, whose paracrine and autocrine production has radioactivity followed by a radioactivity plateau, with some already been mentioned, act as mitogens, growth and anti- oscillations around the average plateau value.
    [Show full text]
  • Vasoactive Intestinal Peptide Inhibits Human Small-Cell Lung Cancer Proliferation in Vitro and in Vivo (Neuropeptides͞camp͞cell Culture͞athymic Nude Mice)
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 14373–14378, November 1998 Medical Sciences Vasoactive intestinal peptide inhibits human small-cell lung cancer proliferation in vitro and in vivo (neuropeptidesycAMPycell cultureyathymic nude mice) KANAME MARUNO*, AFAF ABSOOD†, AND SAMI I. SAID‡ Department of Medicine, Northport Veterans Affairs Medical Center Stony Brook, NY 11768-2290, and State University of New York, Health Sciences Center 17-040, Stony Brook, NY 11794-8172 Communicated by Susan E. Leeman, Boston University School of Medicine, Boston, MA, September 23, 1998 (received for review March 15, 1998) ABSTRACT Small-cell lung carcinoma (SCLC) is an ag- cell lines (7, 8). The cells were maintained in RPMI medium gressive, rapidly growing and metastasizing, and highly fatal 1640 containing 10 nM hydrocortisone, 5.0 mgyml insulin, 10 neoplasm. We report that vasoactive intestinal peptide inhib- mgyml transferrin, 10 nM 17b-estradiol, 30 nM sodium selen- its the proliferation of SCLC cells in culture and dramatically ite, 100 unitsyml penicillin, and 100 mgyml streptomycin suppresses the growth of SCLC tumor-cell implants in athy- (HITES medium; ref. 9). As a control, the SCLC cell line mic nude mice. In both cases, the inhibition was mediated NCI-H128 (American Type Culture Collection), which lacks apparently by a cAMP-dependent mechanism, because the VIP receptors (10), was also tested. The cells were incubated inhibition was enhanced by the adenylate cyclase activator in tissue-culture flasks in a humidified atmosphere of 5% CO2 forskolin and the phosphodiesterase inhibitor 3-isobutyl-1- in air at 37°C and grown as floating cell aggregates.
    [Show full text]
  • Secretin and Autism: a Clue but Not a Cure
    SCIENCE & MEDICINE Secretin and Autism: A Clue But Not a Cure by Clarence E. Schutt, Ph.D. he world of autism has been shaken by NBC’s broadcast connections could not be found. on Dateline of a film segment documenting the effect of Tsecretin on restoring speech and sociability to autistic chil- The answer was provided nearly one hundred years ago by dren. At first blush, it seems unlikely that an intestinal hormone Bayless and Starling, who discovered that it is not nerve signals, regulating bicarbonate levels in the stomach in response to a but rather a novel substance that stimulates secretion from the good meal might influence the language centers of the brain so cells forming the intestinal mucosa. They called this substance profoundly. However, recent discoveries in neurobiology sug- “secretin.” They suggested that there could be many such cir- gest several ways of thinking about the secretin-autism connec- culating substances, or molecules, and they named them “hor- tion that could lead to the breakthroughs we dream about. mones” based on the Greek verb meaning “to excite”. As a parent with more than a decade of experience in consider- A simple analogy might help. If the body is regarded as a commu- ing a steady stream of claims of successful treatments, and as a nity of mutual service providers—the heart and muscles are the pri- scientist who believes that autism is a neurobiological disorder, I mary engines of movement, the stomach breaks down foods for have learned to temper my hopes about specific treatments by distribution, the liver detoxifies, and so on—then the need for a sys- seeing if I could construct plausible neurobiological mechanisms tem of messages conveyed by the blood becomes clear.
    [Show full text]
  • Bombesin Receptors in Distinct Tissue Compartments of Human Pancreatic Diseases Achim Fleischmann, Ursula Läderach, Helmut Friess, Markus W
    0023-6837/00/8012-1807$03.00/0 LABORATORY INVESTIGATION Vol. 80, No. 12, p. 1807, 2000 Copyright © 2000 by The United States and Canadian Academy of Pathology, Inc. Printed in U.S.A. Bombesin Receptors in Distinct Tissue Compartments of Human Pancreatic Diseases Achim Fleischmann, Ursula Läderach, Helmut Friess, Markus W. Buechler, and Jean Claude Reubi Division of Cell Biology and Experimental Cancer Research (AF, UL, JCR), Institute of Pathology, University of Berne, and Department of Visceral and Transplantation Surgery (HF, MWB), Inselspital, University of Berne, Berne, Switzerland SUMMARY: Overexpression of receptors for regulatory peptides in various human diseases is reportedly of clinical interest. Among these peptides, bombesin and gastrin-releasing peptide (GRP) have been shown to play a physiological and pathophysiological role in pancreatic tissues. Our aim has been to localize bombesin receptors in the human diseased pancreas to identify potential clinical applications of bombesin analogs in this tissue. The presence of bombesin receptor subtypes has been evaluated in specimens of human pancreatic tissues with chronic pancreatitis (n ϭ 23) and ductal pancreatic carcinoma (n ϭ 29) with in vitro receptor autoradiography on tissue sections incubated with 125I-[Tyr4]-bombesin or the universal ligand 125I-[D-Tyr6, ␤-Ala11, Phe13, Nle14]-bombesin(6–14) as radioligands and displaced by subtype-selective bombesin receptor agonists and antagonists. GRP receptors were identified in the pancreatic exocrine parenchyma in 17 of 20 cases with chronic pancreatitis. No measurable bombesin receptors were found in the tumor tissue of ductal pancreatic carcinomas, however, GRP receptors were detected in a subset of peritumoral small veins in 19 of 29 samples.
    [Show full text]
  • Targeting Neuropeptide Receptors for Cancer Imaging and Therapy: Perspectives with Bombesin, Neurotensin, and Neuropeptide-Y Receptors
    Journal of Nuclear Medicine, published on September 4, 2014 as doi:10.2967/jnumed.114.142000 CONTINUING EDUCATION Targeting Neuropeptide Receptors for Cancer Imaging and Therapy: Perspectives with Bombesin, Neurotensin, and Neuropeptide-Y Receptors Clément Morgat1–3, Anil Kumar Mishra2–4, Raunak Varshney4, Michèle Allard1,2,5, Philippe Fernandez1–3, and Elif Hindié1–3 1CHU de Bordeaux, Service de Médecine Nucléaire, Bordeaux, France; 2University of Bordeaux, INCIA, UMR 5287, Talence, France; 3CNRS, INCIA, UMR 5287, Talence, France; 4Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, DRDO, New Delhi, India; and 5EPHE, Bordeaux, France Learning Objectives: On successful completion of this activity, participants should be able to list and discuss (1) the presence of bombesin receptors, neurotensin receptors, or neuropeptide-Y receptors in some major tumors; (2) the perspectives offered by radiolabeled peptides targeting these receptors for imaging and therapy; and (3) the choice between agonists and antagonists for tumor targeting and the relevance of various PET radionuclides for molecular imaging. Financial Disclosure: The authors of this article have indicated no relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through October 2017.
    [Show full text]
  • Small Cell Lung Cancer Cells: Stimulation by Multiple Neuropeptides and Inhibition by Broad Spectrum Antagonists
    SMALL CELL LUNG CANCER CELLS: STIMULATION BY MULTIPLE NEUROPEPTIDES AND INHIBITION BY BROAD SPECTRUM ANTAGONISTS. A thesis submitted for the degree of Doctor of Philosophy in the University of London by TARIQJ. SETHI July 1993 Growth Regulation Laboratory Department of Cell Biology Imperial Cancer Research Fund University College London London ProQuest Number: 10017254 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10017254 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 ABSTRACT Human small cell lung cancer (SCLC) constitutes 25% of lung cancers and follows an aggressive clinical course. SCLC is characterised by the presence of intracytoplasmic neurosecretory granules and by its ability to secrete many hormones and neuropeptides. Only bombesin-like peptides, which include gastrin-releasing peptide (GRP), have been shown to act as autocrine growth factors for certain SCLC cell lines. This thesis focused on other neuropeptides and particularly their ability to mediate SCLC growth. The neuropeptides bradykinin, cholecystokinin (CCK), GRP, neurotensin and vasopressin at nanomolar concentrations stimulated an increase in the intracellular concentration of calcium ([Ca^+Jj), inositol phosphate hydrolysis, and increased colony formation in semi-solid medium in responsive SCLC cell lines.
    [Show full text]
  • Growth Hormone-Releasing Hormone in Lung Physiology and Pulmonary Disease
    cells Review Growth Hormone-Releasing Hormone in Lung Physiology and Pulmonary Disease Chongxu Zhang 1, Tengjiao Cui 1, Renzhi Cai 1, Medhi Wangpaichitr 1, Mehdi Mirsaeidi 1,2 , Andrew V. Schally 1,2,3 and Robert M. Jackson 1,2,* 1 Research Service, Miami VAHS, Miami, FL 33125, USA; [email protected] (C.Z.); [email protected] (T.C.); [email protected] (R.C.); [email protected] (M.W.); [email protected] (M.M.); [email protected] (A.V.S.) 2 Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33101, USA 3 Department of Pathology and Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33101, USA * Correspondence: [email protected]; Tel.: +305-575-3548 or +305-632-2687 Received: 25 August 2020; Accepted: 17 October 2020; Published: 21 October 2020 Abstract: Growth hormone-releasing hormone (GHRH) is secreted primarily from the hypothalamus, but other tissues, including the lungs, produce it locally. GHRH stimulates the release and secretion of growth hormone (GH) by the pituitary and regulates the production of GH and hepatic insulin-like growth factor-1 (IGF-1). Pituitary-type GHRH-receptors (GHRH-R) are expressed in human lungs, indicating that GHRH or GH could participate in lung development, growth, and repair. GHRH-R antagonists (i.e., synthetic peptides), which we have tested in various models, exert growth-inhibitory effects in lung cancer cells in vitro and in vivo in addition to having anti-inflammatory, anti-oxidative, and pro-apoptotic effects. One antagonist of the GHRH-R used in recent studies reviewed here, MIA-602, lessens both inflammation and fibrosis in a mouse model of bleomycin lung injury.
    [Show full text]
  • Inhibition of Gastrin Release by Secretin Is Mediated by Somatostatin in Cultured Rat Antral Mucosa
    Inhibition of gastrin release by secretin is mediated by somatostatin in cultured rat antral mucosa. M M Wolfe, … , G M Reel, J E McGuigan J Clin Invest. 1983;72(5):1586-1593. https://doi.org/10.1172/JCI111117. Research Article Somatostatin-containing cells have been shown to be in close anatomic proximity to gastrin-producing cells in rat antral mucosa. The present studies were directed to examine the effect of secretin on carbachol-stimulated gastrin release and to assess the potential role of somatostatin in mediating this effect. Rat antral mucosa was cultured at 37 degrees C in Krebs-Henseleit buffer, pH 7.4, gassed with 95% O2-5% CO2. After 1 h the culture medium was decanted and mucosal gastrin and somatostatin were extracted. Carbachol (2.5 X 10(-6) M) in the culture medium increased gastrin level in the medium from 14.1 +/- 2.5 to 26.9 +/- 3.0 ng/mg tissue protein (P less than 0.02), and decreased somatostatin-like immunoreactivity in the medium from 1.91 +/- 0.28 to 0.62 +/- 0.12 ng/mg (P less than 0.01) and extracted mucosal somatostatin-like immunoreactivity from 2.60 +/- 0.30 to 1.52 +/- 0.16 ng/mg (P less than 0.001). Rat antral mucosa was then cultured in the presence of secretin to determine its effect on carbachol-stimulated gastrin release. Inclusion of secretin (10(-9)-10(-7) M) inhibited significantly carbachol-stimulated gastrin release into the medium, decreasing gastrin from 26.9 +/- 3.0 to 13.6 +/- 3.2 ng/mg (10(-9) M secretin) (P less than 0.05), to 11.9 +/- 1.7 ng/mg (10(-8) secretin) (P less than 0.02), and to 10.8 +/- 4.0 ng/mg (10(-7) M secretin) (P less than […] Find the latest version: https://jci.me/111117/pdf Inhibition of Gastrin Release by Secretin Is Mediated by Somatostatin in Cultured Rat Antral Mucosa M.
    [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]
  • The Role of Corticotropin-Releasing Hormone at Peripheral Nociceptors: Implications for Pain Modulation
    biomedicines Review The Role of Corticotropin-Releasing Hormone at Peripheral Nociceptors: Implications for Pain Modulation Haiyan Zheng 1, Ji Yeon Lim 1, Jae Young Seong 1 and Sun Wook Hwang 1,2,* 1 Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea; [email protected] (H.Z.); [email protected] (J.Y.L.); [email protected] (J.Y.S.) 2 Department of Physiology, College of Medicine, Korea University, Seoul 02841, Korea * Correspondence: [email protected]; Tel.: +82-2-2286-1204; Fax: +82-2-925-5492 Received: 12 November 2020; Accepted: 15 December 2020; Published: 17 December 2020 Abstract: Peripheral nociceptors and their synaptic partners utilize neuropeptides for signal transmission. Such communication tunes the excitatory and inhibitory function of nociceptor-based circuits, eventually contributing to pain modulation. Corticotropin-releasing hormone (CRH) is the initiator hormone for the conventional hypothalamic-pituitary-adrenal axis, preparing our body for stress insults. Although knowledge of the expression and functional profiles of CRH and its receptors and the outcomes of their interactions has been actively accumulating for many brain regions, those for nociceptors are still under gradual investigation. Currently, based on the evidence of their expressions in nociceptors and their neighboring components, several hypotheses for possible pain modulations are emerging. Here we overview the historical attention to CRH and its receptors on the peripheral nociception and the recent increases in information regarding their roles in tuning pain signals. We also briefly contemplate the possibility that the stress-response paradigm can be locally intrapolated into intercellular communication that is driven by nociceptor neurons.
    [Show full text]
  • Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications
    molecules Review Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications Fanny d’Orlyé, Laura Trapiella-Alfonso , Camille Lescot, Marie Pinvidic, Bich-Thuy Doan and Anne Varenne * Chimie ParisTech PSL, CNRS 8060, Institute of Chemistry for Life and Health (i-CLeHS), 75005 Paris, France; [email protected] (F.d.); [email protected] (L.T.-A.); [email protected] (C.L.); [email protected] (M.P.); [email protected] (B.-T.D.) * Correspondence: [email protected]; Tel.: +33-1-8578-4252 Abstract: There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on Citation: d’Orlyé, F.; the nature and sequence of the amino acids that constitute them.
    [Show full text]
  • Interactions Between Two Different G Protein-Coupled Receptors in Reproductive Hormone-Producing Cells: the Role of PACAP and Its Receptor PAC1R
    International Journal of Molecular Sciences Review Interactions between Two Different G Protein-Coupled Receptors in Reproductive Hormone-Producing Cells: The Role of PACAP and Its Receptor PAC1R Haruhiko Kanasaki *, Aki Oride, Tomomi Hara, Tselmeg Mijiddorj, Unurjargal Sukhbaatar and Satoru Kyo Department of Obstetrics and Gynecology, School of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan; [email protected] (A.O.); [email protected] (T.H.); [email protected] (T.M.); [email protected] (U.S.); [email protected] (S.K.) * Correspondence: [email protected]; Tel.: +81-853-20-2268; Fax: +81-853-20-2264 Academic Editor: Kathleen Van Craenenbroeck Received: 18 August 2016; Accepted: 19 September 2016; Published: 26 September 2016 Abstract: Gonadotropin-releasing hormone (GnRH) and gonadotropins are indispensable hormones for maintaining female reproductive functions. In a similar manner to other endocrine hormones, GnRH and gonadotropins are controlled by their principle regulators. Although it has been previously established that GnRH regulates the synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)—both gonadotropins—from pituitary gonadotrophs, it has recently become clear that hypothalamic GnRH is under the control of hypothalamic kisspeptin. Prolactin, which is also known as luteotropic hormone and is released from pituitary lactotrophs, stimulates milk production in mammals. Prolactin is also regulated by hypothalamic factors, and it is thought that prolactin synthesis and release are principally under inhibitory control by dopamine through the dopamine D2 receptor. In addition, although it remains unknown whether it is a physiological regulator, thyrotropin-releasing hormone (TRH) is a strong secretagogue for prolactin.
    [Show full text]