Neuropeptides
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Calcitonin Gene Products and the Kidney
Kiinische Klin Wochenschr (1989) 67:870-875 W°chenchrif t © Springer-Verlag 1989 Calcitonin Gene Products and the Kidney A. Kurtz 1, R. Muff z, and J.A. Fischer z 1 Physiologic Institute, University of Ziirich, Switzerland 2 Research Laboratory for Calcium Metabolism, Departments of Orthopedic Surgery and Medicine, University of Ziirich, Ziirich, Switzerland Summary. Calcitonin gene-related peptide (CGRP) Calcitonin and CGRP are single chain polypep- is localized in capsaicin-sensitive nerve fibres in the tides consisting of 32 and 37 amino acids, respec- kidney and urogenital tract whereas calcitonin tively. They have in common amino-terminal ring reaches the kidney through the general circulation. structures linked by disulfide bridges and the car- Systemic infusion of CGRP and perfusion of iso- boxyltermini are amidated. In man, CGRP shares lated rat kidney reduces vascular resistance, and 16% structural homology with calcitonin whereas increases renal blood flow and glomerular filtra- the homology between CGRP-I and -II is 92% tion. CGRP stimulates renin secretion in vivo and [13]. As a result, distinct receptors for calcitonin in vitro and inhibits contraction of isolated rat me- and CGRP have been identified [7, 11, 33, 42]. sangial cells by angiotensin II. Calcitonin does not Human CGRP-I and -II, due to their high homolo- affect vascular resistance, renal blood flow and glo- gy, crossreact almost completely, but subtle differ- merular filtration, and is tess potent in stimulating ences in the distribution of human CGRP-I and renin secretion, and does not alter contraction of -II binding sites have been observed on receptor isolated rat mesangial cells by angiotensin II. -
Neurotensin Activates Gabaergic Interneurons in the Prefrontal Cortex
The Journal of Neuroscience, February 16, 2005 • 25(7):1629–1636 • 1629 Behavioral/Systems/Cognitive Neurotensin Activates GABAergic Interneurons in the Prefrontal Cortex Kimberly A. Petrie,1 Dennis Schmidt,1 Michael Bubser,1 Jim Fadel,1 Robert E. Carraway,2 and Ariel Y. Deutch1 1Departments of Pharmacology and Psychiatry, Vanderbilt University Medical Center, Nashville, Tennessee 37212, and 2Department of Physiology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655 Converging data suggest a dysfunction of prefrontal cortical GABAergic interneurons in schizophrenia. Morphological and physiological studies indicate that cortical GABA cells are modulated by a variety of afferents. The peptide transmitter neurotensin may be one such modulator of interneurons. In the rat prefrontal cortex (PFC), neurotensin is exclusively localized to dopamine axons and has been suggested to be decreased in schizophrenia. However, the effects of neurotensin on cortical interneurons are poorly understood. We used in vivo microdialysis in freely moving rats to assess whether neurotensin regulates PFC GABAergic interneurons. Intra-PFC administra- tion of neurotensin concentration-dependently increased extracellular GABA levels; this effect was impulse dependent, being blocked by treatment with tetrodotoxin. The ability of neurotensin to increase GABA levels in the PFC was also blocked by pretreatment with 2-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazole-3-yl)carbonylamino]tricyclo(3.3.1.1.3.7)decan-2-carboxylic acid (SR48692), a high-affinity neurotensin receptor 1 (NTR1) antagonist. This finding is consistent with our observation that NTR1 was localized to GABAergic interneurons in the PFC, particularly parvalbumin-containing interneurons. Because neurotensin is exclusively localized to dopamine axons in the PFC, we also determined whether neurotensin plays a role in the ability of dopamine agonists to increase extracellular GABA levels. -
Purification of a Galanin Receptor from Pig Brain
Proc. Natl. Acad. Sci. USA Vol. 90, pp. 3845-3849, May 1993 Neurobiology Purification of a galanin receptor from pig brain YAOHUI CHEN*, ALAIN FOURNIERt, ALAIN COUVINEAU*, MARC LABURTHE*, AND BRIGITTE AMIRANOFF*t *Laboratoire de Biologie and Physiologie des Cellules Digestives, Institut National de la Sant6 et de la Recherche Mddicale, U 239, 16 Rue Henri Huchard-75018 Paris, France; and tUniversitd du Quebec, Institut National de la Recherche Scientifique, INRS-Santd, 245 Boulevard Hymus, Pointe Claire, Qudbec, H9R1G6, Canada Communicated by Tomas Hokfelt, January 4, 1993 ABSTRACT A galanin receptor protein was solubilized lished data), we report the purification of a galanin receptor with 3-[(3-cholamidopropyl)dimethylammonio]-1-propane- from pig brain, a rich source of receptors that is available in sulfonate (CHAPS) from pig brain membranes and then pu- large amounts. This represents a basic step toward knowl- rified by single-step affinity chromatography. The product edge of the pharmacology and biochemistry of galanin re- exhibits saturable and specific binding for galanin with a ceptors and should lead to a better understanding of their binding activity of 17 nmol/mg of protein and a dissociation expression in the organism. constant (Kd) of 10 nM. This represents a 300,000-fold puri- fication over the detergent-solubilized fraction with a final recovery of 31% of the initial membrane galanin binding METHODS activity. Gel electrophoresis of the affinity-purified material Materials. Synthetic porcine galanin, glucagon, vasoactive showed a single polypeptide of 54 kDa by silver staining and intestinal peptide, synthetic neurotensin, substance P, baci- after radioiodination. Cross-linking of a purified fraction af- tracin, leupeptin, pepstatin A, GTP, GDP, guanosine 5'-[13,v- rmity-labeled with 125I-labeled galanin revealed a single band imido]triphosphate, cholesteryl hemisuccinate, 3-[(3-cholami- for the galanin-receptor complex at 57 kDa. -
And Neurotensin-Immunoreactive Cells in the Gastrointestinal Tract of the Chicken
Histol Histopath (1989) 4: 55-62 Histology and Histopathology The distribution and ontogeny of gastrin/CCK-, somatostatin- and neurotensin-immunoreactive cells in the gastrointestinal tract of the chicken B.C. Alison Department of Anatomy, Medical School, University of the Witwatersrand,Johannesburg, South Africa Summary. The distribution and time of appearance of wide variety of invertebrates and of vertebrates, cells with gastrin1CCK-, neurotensin- and somatostatin- especially mammals, (Rufener et al., 1975; Sundler et like immunoreactivity were studied in samples from al., 1977; Alumets et al., 1977; Helmstaedter et al., 1977; eight regions of the gastrointestinal tract of chick Seino et al., 1979). Studies on avian gut have been embryos from 11 days of incubation to hatching. No conducted at hatching (Rawdon and Andrew, 1981) and immunoreactive cells were found in any region at 11 thereafter in young birds, (Larsson et al., 1974) and days of incubation. Somatostatin- and neurotensin- adults (Aitken, 1958; Yamada et al., 1979). immunoreactive cells appeared for the first time in the Immunocytochemical studies have also demonstrated proventriculus, pyloric region and duodenum at 12 days immunoreactive cells of various types in early rat and of incubation with cells immunoreactive for neurotensin human foetal gut (Larsson et al., 1975; Dubois et al., occurring in the rectum at the same stage. GastrinICCK- 1976; Dubois et al., 1976; Larsson et al., 1977; Dupouy et immunoreactive cells were detected in the small intestine al., 1983; Kataoka et al., 1985). There is, however, much first at 14 days and in the pyloric region two days later. less published work on embryonic avian material; that of Cells immunoreactive for somatostatin and neurotensin Sundler et al. -
Neurotransmitter and Neuropeptide Regulation of Mast Cell Function
Xu et al. Journal of Neuroinflammation (2020) 17:356 https://doi.org/10.1186/s12974-020-02029-3 REVIEW Open Access Neurotransmitter and neuropeptide regulation of mast cell function: a systematic review Huaping Xu1, Xiaoyun Shi2, Xin Li3, Jiexin Zou4, Chunyan Zhou5, Wenfeng Liu5, Huming Shao5, Hongbing Chen5 and Linbo Shi4* Abstract The existence of the neural control of mast cell functions has long been proposed. Mast cells (MCs) are localized in association with the peripheral nervous system (PNS) and the brain, where they are closely aligned, anatomically and functionally, with neurons and neuronal processes throughout the body. They express receptors for and are regulated by various neurotransmitters, neuropeptides, and other neuromodulators. Consequently, modulation provided by these neurotransmitters and neuromodulators allows neural control of MC functions and involvement in the pathogenesis of mast cell–related disease states. Recently, the roles of individual neurotransmitters and neuropeptides in regulating mast cell actions have been investigated extensively. This review offers a systematic review of recent advances in our understanding of the contributions of neurotransmitters and neuropeptides to mast cell activation and the pathological implications of this regulation on mast cell–related disease states, though the full extent to which such control influences health and disease is still unclear, and a complete understanding of the mechanisms underlying the control is lacking. Future validation of animal and in vitro models also is needed, which incorporates the integration of microenvironment-specific influences and the complex, multifaceted cross-talk between mast cells and various neural signals. Moreover, new biological agents directed against neurotransmitter receptors on mast cells that can be used for therapeutic intervention need to be more specific, which will reduce their ability to support inflammatory responses and enhance their potential roles in protecting against mast cell–related pathogenesis. -
Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors
Physiol Rev 92: 1699–1775, 2012 doi:10.1152/physrev.00048.2010 SENSORY AND SIGNALING MECHANISMS OF BRADYKININ, EICOSANOIDS, PLATELET-ACTIVATING FACTOR, AND NITRIC OXIDE IN PERIPHERAL NOCICEPTORS Gábor Peth˝o and Peter W. Reeh Pharmacodynamics Unit, Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Pécs, Hungary; and Institute of Physiology and Pathophysiology, University of Erlangen/Nürnberg, Erlangen, Germany Peth˝o G, Reeh PW. Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors. Physiol Rev 92: 1699–1775, 2012; doi:10.1152/physrev.00048.2010.—Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation Lor excitation by these substances of nociceptive nerve endings or fibers implicates generation of action potentials which then travel to the central nervous system and may induce pain sensation. Sensitization of nociceptors refers to their increased responsiveness to either thermal, mechani- cal, or chemical stimuli that may be translated to corresponding hyperalgesias. This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons. Manifestations, receptor molecules, and intracellular signaling mechanisms -
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. -
Calcitonin Gene-Related Peptide Inhibits Local Acute Inflammation and Protects Mice Against Lethal Endotoxemia
SHOCK, Vol. 24, No. 6, pp. 590–594, 2005 CALCITONIN GENE-RELATED PEPTIDE INHIBITS LOCAL ACUTE INFLAMMATION AND PROTECTS MICE AGAINST LETHAL ENDOTOXEMIA Rachel Novaes Gomes,* Hugo C. Castro-Faria-Neto,* Patricia T. Bozza,* Milena B. P. Soares,† Charles B. Shoemaker,‡ John R. David,§ and Marcelo T. Bozza{ *Laborato´rio de Imunofarmacologia, Departamento de Fisiologia e Farmacodinaˆmica, Fundacxa˜o Oswaldo Cruz, Rio de Janeiro 21045-900; †Centro de Pesquisas Goncxalo Muniz, Fundacxa˜o Oswaldo Cruz, Salvador/Bahia 40295-001; ‡Division of Infectious Diseases, Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, North Grafton, Massachusettes; §Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusettes; {Laborato´rio de Inflamacxa˜o e Imunidade, Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro 21941-590, Rio de Janeiro, Brazil Received 2 Sep 2004; first review completed 15 Sep 2004; accepted in final form 10 Aug 2005 ABSTRACT—Calcitonin gene-related peptide (CGRP), a potent vasodilatory peptide present in central and peripheral neurons, is released at inflammatory sites and inhibits several macrophage, dendritic cell, and lymphocyte functions. In the present study, we investigated the role of CGRP in models of local and systemic acute inflammation and on macrophage activation induced by lipopolysaccharide (LPS). Intraperitoneal pretreatment with synthetic CGRP reduces in approximately 50% the number of neutrophils in the blood and into the peritoneal cavity 4 h after LPS injection. CGRP failed to inhibit neutrophil recruitment induced by the direct chemoattractant platelet-activating factor, whereas it significantly inhibited LPS- induced KC generation, suggesting that the effect of CGRP on neutrophil recruitment is indirect, acting on chemokine production by resident cells. -
Predicting Cell-Penetrating Peptides Using Machine Learning Algorithms and Navigating in Their Chemical Space
www.nature.com/scientificreports OPEN Predicting cell‑penetrating peptides using machine learning algorithms and navigating in their chemical space Ewerton Cristhian Lima de Oliveira 1, Kauê Santana 2*, Luiz Josino 3, Anderson Henrique Lima e Lima 3* & Claudomiro de Souza de Sales Júnior 1* Cell‑penetrating peptides (CPPs) are naturally able to cross the lipid bilayer membrane that protects cells. These peptides share common structural and physicochemical properties and show diferent pharmaceutical applications, among which drug delivery is the most important. Due to their ability to cross the membranes by pulling high‑molecular‑weight polar molecules, they are termed Trojan horses. In this study, we proposed a machine learning (ML)‑based framework named BChemRF‑ CPPred (beyond chemical rules-based framework for CPP prediction) that uses an artifcial neural network, a support vector machine, and a Gaussian process classifer to diferentiate CPPs from non‑CPPs, using structure‑ and sequence‑based descriptors extracted from PDB and FASTA formats. The performance of our algorithm was evaluated by tenfold cross‑validation and compared with those of previously reported prediction tools using an independent dataset. The BChemRF‑CPPred satisfactorily identifed CPP‑like structures using natural and synthetic modifed peptide libraries and also obtained better performance than those of previously reported ML‑based algorithms, reaching the independent test accuracy of 90.66% (AUC = 0.9365) for PDB, and an accuracy of 86.5% (AUC = 0.9216) for FASTA input. Moreover, our analyses of the CPP chemical space demonstrated that these peptides break some molecular rules related to the prediction of permeability of therapeutic molecules in cell membranes. -
In the Mammalian and Avian Gastrointestinal Tract
Gut: first published as 10.1136/gut.15.9.720 on 1 September 1974. Downloaded from Gut, 1974, 15, 720-724 Cellular localization of a vasoactive intestinal peptide in the mammalian and avian gastrointestinal tract JULIA M. POLAK, A. G. E. PEARSE, J-C. GARAUD, AND S. R. BLOOM From the Department ofHistochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, London, and the Institute of Clinical Research, Middlesex Hospital, London SUMMARY Immunohistochemical studies using an antiserum to a pure porcine vasoactive intestinal peptide, possessing no cross reactivity against the related hormones glucagon, secretin, and gastrin- inhibitory peptide, revealed a wide distribution of vasoactive intestinal peptide cells throughout the entire length of the mammalian and avian gut. The highest numbers of cells were present in the small intestine and more particularly in the large intestine in all species investigated. Three types of endocrine cell in the mammalian gut are sufficiently widely distributed to be con- sidered as the sites for production of vasoactive intestinal peptide. In the avian gut there are only two identifiable cell types. Sequential immunofluorescence and silver staining showed, in the bird, that the enterochromaffin (EC) cell was not responsible. This procedure could not be used in our mammalian gut samples but here serial section immunofluorescence for enteroglucagon and vasoactive intestinal peptide in- dicated that the two cells were not identical and that each was differently localized in the mucosa. These results leave the D cell of the Wiesbaden classification as the most likely site for the produc- tion of vasoactive intestinal peptide. The final identification must come from successful immune electron cytochemistry but this has not yet been achieved. -
Developmental Expression Oe Neurotensin and Galanin In
Biomedical Research 16 (5) 281-286, 1995 i 1| i 2 DEVELOPMENTAL EXPRESSION OE NEUROTENSIN AND GALANIN § IN THE RAT GASTROINTESTINAL TRACT 2 i i MUNEO OKA‘, NIMA KHANDAN-—NIA2, PHILIP JoNEs2, MOHAMMAD GHATEI2 and STEPHEN ROBERT BLOOM2 ‘Department of Endocrinology, Internal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi 321-02, Japan, and 2Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 ONN, U.K. ABSTRACT To characterize and compare the developmental patterns of neurotensin (NT) and galanin (GAL) expression in the gastrointestinal tract, we measured both peptide content and mRNA concentrations in different regions of the rat gastrointestinal tract at different times during fetal and postnatal development. The abundance of NT mRNA in the jejunum and ileum increased from birth and peaked on day 7, subsequently decreased by day 21. In con- trast, expression of NT mRNA in the stomach and colon remained very low. Changes in NT peptide content parallelled that in NT mRNA. On the other hand, the abundance of GAL mRNA, which was expressed in all regions of the gastrointestinal tract, gradually increased until day 21 following birth. GAL peptide content increased up until day 7; thereafter, the levels of this peptide remained relatively unchanged. Thus, the gene expres- sion of NT and GAL each demonstrates a specific pattern of tissue distribution and a dif- ferent developmental pattern. These data suggest that NT and GAL gene expression and peptide content are developmentally regulated and that NT and GAL each play a different role in the gastrointestinal tract during development. Previous studies have suggested important roles for distribution of these neuropeptides during gut several neuropeptides in maintaining the functional development should provide a better understanding and structural integrity of the gut. -
Galanin, Neurotensin, and Phorbol Esters Rapidly Stimulate Activation of Mitogen-Activated Protein Kinase in Small Cell Lung Cancer Cells
[CANCER RESEARCH 56. 5758-5764, December 15, 1996] Galanin, Neurotensin, and Phorbol Esters Rapidly Stimulate Activation of Mitogen-activated Protein Kinase in Small Cell Lung Cancer Cells Thomas Seufferlein and Enrique Rozengurt' Imperial Cancer Research Fund, P. 0. Box 123, 44 Lincoln ‘sinnFields, London WC2A 3PX, United Kingdom ABSTRACT and p44me@@k,aredirectly activated by phosphorylation on specific tyrosine and threonine residues by the dual-specificity MEKs, of Addition of phorbol 12,13-dibutyrate (PDB) to H 69, H 345, and H 510 which at least two isofonus, MEK-1 and MEK-2, have been identified small cell lung cancer (SCLC) cells led to a rapid concentration- and in mammalian cells (12—14).Several pathways leading to MEK acti time-dependent increase in p42―@ activity. PD 098059 [2-(2'-amino 3'-methoxyphenyl)-oxanaphthalen-4-one], a selective inhibitor of mitogen vation have been described. Tyrosine kinase receptors induce p42r@a@@@( activated protein kinase (MAPK) kinase 1, prevented activation of via a son of sevenless (SOS)-mediated accumulation of p2l@-GTP, p42maPk by PDB in SCLC cells. PDB also stimulated the activation of which then activates a kinase cascade comprising p74@', MEK, and p90r$k, a major downstream target of p42―@. The effect of PDB on both p42Jp44maPk (10, 11). Activation of seven transmembrane domain p42―@and p90rsk activation could be prevented by down-regulation of receptors also leads to p42@'@ activation, but the mechanisms in protein kinase C (PKC) by prolonged pretreatment with 800 aM PDB or volved are less clear, although both p2l@- and PKC-dependent treatment of SCLC cells with the PKC inhibitor bisindolylmaleinside (GF pathways have been implicated (15—20).Activated MAPKs directly 109203X), demonstrating the involvement ofphorbol ester-sensitive PKCS phosphorylate and activate various enzymes, e.g., p90@ (21, 22), and In the signaling pathway leading to p42 activation.