DOCSLIB.ORG

Pituitary Actions of Rfamide Peptides: a Critique of the Evidence

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pituitary Actions of Rfamide Peptides: a Critique of the Evidence The Open Neuroendocrinology Journal, 2011, 4, 51-63 51 Open Access Pituitary Actions of RFamide Peptides: A Critique of the Evidence Greg M. Anderson* Centre for Neuroendocrinology and Department of Anatomy and Structural Biology, University of Otago School of Medical Sciences, PO Box 913, Dunedin 9054, New Zealand Abstract: RFamides are a relatively recently-discovered class of peptides characterised by an arginine-phenylalanine- amide at their C terminus. In mammals, all of the five known RFamide families (neuropeptide FFs, prolactin-releasing peptides, RFamide-related peptides, kisspeptins and pyroglutamylated RFs) were originally discovered as neuropeptides influencing central nervous system functions such as reproduction, feeding behavior and nociception; however presence of their G-protein-coupled receptors in the pituitary gland has led to speculation that they also influence the function of this gland by either autocrine/paracrine or neuroendocrine mechanisms. In support of such actions, prolactin-releasing peptide is produced locally within the pituitary gland, and pulses of neuropeptide FF are secreted into blood from nerve terminals in the posterior pituitary lobe originating from the hypothalamus. In contrast, it is argued that the balance of ex- perimental evidence does not yet support such roles for RFamide-related peptides, kisspeptins and pyroglutamylated RF peptides due to their absence or scarcity in the neurosecretory zone of the median eminence, blood and pituitary tissue. In some cases, assignment of functional nomenclature has been based on inconclusive evidence of the proposed function, causing confusion in the field. To resolve these issues it will be important to compare the peptide concentrations required to elicit pituitary effects with those found in portal and peripheral blood and in pituitary tissue. To date this has only been systematically done for kisspeptin, for which the portal blood concentration was found to be several orders of magnitude lower than that which stimulated gonadotrophin release from primary pituitary cell cultures. Keywords: RFamide, NPFF, NPAF, PrRP, RFRP, GnIH, kisspeptin, QRFP, 26RFa, pituitary. INTRODUCTION external zone of the hypothalamic median eminence and carried to the anterior pituitary gland by the portal blood RFamides form a class of neuropeptides characterized by system) mechanisms. RFamide peptides have been an arginine-phenylalanine-amide motif at their C terminus. implicated in the regulation of almost all of the major They were first identified in 1977 in molluscan cerebral pituitary hormones, including prolactin, luteinising hormone ganglia [1], but almost another decade passed before they (LH), follicle stimulating hormone (FSH), growth hormone, were purified and chemically characterised in any adrenocorticotrophic hormone (ACTH), oxytocin and mammalian species [2]. There are now five RFamide arginine vasopressin (AVP), although some of these are families known to exist in the mammalian central nervous likely to be regulated indirectly via other hypophysiotrophic system, where their widespread fibre distribution implies regulatory hormones. Thus, their sphere of influence on varied roles including regulation of energy balance, endocrine functions is likely to include maternal physiology, behaviour and reproduction [3, 4]. In particular, at least four reproduction, growth, stress responses, diuresis and blood of the five known mammalian genes encoding RFamide pressure regulation. In two cases where the evidence for peptides have been shown to influence food intake [5]. hypophysiotrophic effects is not compelling (PrRP and Grouped by the precursor peptides that encompass the RFRP, sometimes known as gonadotrophin-inhibitory mature RFamide peptides and listed in order of their date of hormone), the peptide nomenclature nevertheless reflects this isolation in mammals, these families are: neuropeptide FF putative mode of action. At present there is a need for a (NPFF) precursor, prolactin-releasing peptide (PrRP) unified and formalised nomenclature for RFamide peptides, precursor, RFamide-related peptide (RFRP) precursor, since some are named after the function initially assigned to kisspeptin precursor and pyroglutamylated RFamide peptide them, others have nomenclature that reflects their molecular (QRFP) precursor (see Table 1 for details). structure, and most have more than one name in common In addition to their diverse roles within the central usage. nervous system, direct pituitary actions have been proposed All mammalian RFamide peptides have been found to be for all mammalian RFamides, either via autocrine/paracrine ligands of formerly 'orphan' G protein-coupled receptors. In or hypophysiotrophic (secreted by nerve terminals in the some cases there is considerable overlap in the binding affinity between different RFamides and their receptors, *Address correspondence to this author at the Centre for Neuroendocrinol- since the receptor selectivity appears to be determined ogy and Department of Anatomy and Structural Biology, University of largely by the few relatively conserved amino acids at the C Otago School of Medical Sciences, PO Box 913, Dunedin 9054, New Zea- terminus [6]. In particular, a number of RFamides show land; Tel: 64 3 4797320; Fax: 64 3 4797254; considerable affinity and agonistic activity to the preferred E-mail: [email protected] 1876-5289/11 2011 Bentham Open 52 The Open Neuroendocrinology Journal, 2011, Volume 4 Greg M. Anderson Table 1. Details of the Known Mammalian RFamides, their Precursor Peptides and G Protein-Coupled Receptors (Alternative Names to those Used in this Manuscript are Shown in Brackets) RFamide Peptide Precursor Peptide Produced by Receptor (Highest Affinity First) Pituitary Reference to Gene Pituitary Gland Receptor Levels Initial Discovery Neuropeptide FF Npff No, but secreted in GPR74 (NPFF2 receptor; + [2] (FMRFamide-related posterior lobe by HLWAR77) + peptide) hypophysiotropic EC50=2-28 nM [7, 27] neurons Neuropeptide AF GPR147 (NPFF1 receptor; OT7T022) EC50=9-10 nM [9, 27] Prolactin-releasing Prrp (Prh) Yes GPR10 (hGR3; UHR-1) ++ [54] peptide 20 EC50=2 nM [7] + Prolactin-releasing GPR74 (NPFF2 receptor; peptide 31 HLWAR77) EC50=170-240 nM [7] RFamide-related Rfrp (Npvf) No GPR147 (NPFF1 receptor; + [9] peptide-1 OT7T022) + (neuropeptide SF) EC50=1-3 nM [7] RFamide-related GPR74 (NPFF2 receptor; peptide-3 HLWAR77) (neuropeptide VF; EC =160-1000 nM [7, 27] gonadotrophin- 50 inhibitory hormone) Kisspeptin 54 Kiss1 Barely detectable GPR54 (OT7T175; AXOR12) + [119-121] mRNA; but EC50=1-7 nM [119] immunoreactivity detected Pyroglutamylated Qrfp (26RFa, P518) Barely detectable GPR103 (AQ27; SP9155) + [15, 160] RFamide peptide 43 mRNA EC50=7 nM (43RFa) 26RFa (P518; QRFP26) receptors for NPFF family members, namely GPR147 and experiments only become meaningful if the minimum GPR74 [7]. The promiscuity of these two receptors may not effective dose of RFamide peptide is lower than the be limited to RFamide peptides, since they also interact concentration measured within the pituitary gland or in moderately with neuropeptide Y (an RYamide) and possibly portal blood; a direct comparison that has been reported for orexin and cholecystokinin peptides, whose function of food kisspeptin [18] but not other RFamide peptides. Where intake regulation overlaps with that of RFamides [7, 8]. hypophysiotrophic mechanisms are suggested, these need to Because of such potential interactions, the location of the be substantiated by testing for uptake by the putative secreted peptides must be considered in relation to that of the hypophysiotrophic neurones of a retrograde tract tracing dye receptors to which they have agonistic activity when from the pituitary gland or systemic circulation [19-21]. attempting to determine their effects at the pituitary level and This purpose of this review is to critique and discuss the at other peripheral sites. RT-PCR measurements concur that merits of the proposed direct pituitary actions for each all of the identified RFamide receptor genes are expressed in RFamide family. The scope is generally limited to the the pituitary gland; albeit usually at low levels [8-15]. The mammalian RFamide peptides; however reference to most commonly utilised approach to determining if RFamide mechanisms of action in other vertebrate classes is made peptides act on the pituitary gland has been to assess their where the comparison is of interest. effects on pituitary hormone secretion in primary pituitary cell cultures. In this review I advocate caution in making NEUROPEPTIDE FF (NPFF) AND NEUROPEPTIDE conclusions about in vivo function based solely on this AF (NPAF) approach, if for no other reason than the fact that receptors The octapeptide NPFF and the structurally related known to be involved in RFamide peptide signalling [16] octadecapeptide NPAF were originally isolated in 1985 from may be expressed in primary cell cultures at levels bovine brain tissue using an antibody raised against the considerably greater than those normally seen in vivo [17]. molluscan peptide FMRFamide [2] and named after their N Furthermore, RFamide effects observed in in vitro Pituitary Actions of RFamide Peptides: a Critique of the Evidence The Open Neuroendocrinology Journal, 2011, Volume 4 53 and C terminal amino acids. They share a common precursor the rat, no NPFF and AVP-immunostained cells were protein containing a single copy of both peptides in mouse, observed in the human supraoptic nuclei in a recent
Load more

Recommended publications
  • Effects of Kisspeptin-13 on the Hypothalamic-Pituitary-Adrenal Axis, Thermoregulation, Anxiety and Locomotor Activity in Rats
    Effects of kisspeptin-13 on the hypothalamic-pituitary-adrenal axis, thermoregulation, anxiety and locomotor activity in rats Krisztina Csabafiª, Miklós Jászberényiª, Zsolt Bagosiª, Nándor Liptáka, Gyula Telegdyª,b a Department of Pathophysiology, University of Szeged, P.O. Box 427, H-6701Szeged, Hungary b Neuroscience Research Group of the Hungarian Academy of Sciences, P.O. Box 521, H- 6701Szeged, Hungary Corresponding author: Krisztina Csabafi MD Department of Pathophysiology, University of Szeged H-6701 Szeged, Semmelweis u. 1, PO Box: 427 Hungary Tel.:+ 36 62 545994 Fax: + 36 62 545710 E-mail: [email protected] 1 Abstract Kisspeptin is a mammalian amidated neurohormone, which belongs to the RF-amide peptide family and is known for its key role in reproduction. However, in contrast with the related members of the RF-amide family, little information is available regarding its role in the stress-response. With regard to the recent data suggesting kisspeptin neuronal projections to the paraventricular nucleus, in the present experiments we investigated the effect of kisspeptin-13 (KP-13), an endogenous derivative of kisspeptin, on the hypothalamus- pituitary-adrenal (HPA) axis, motor behavior and thermoregulatory function. The peptide was administered intracerebroventricularly (icv.) in different doses (0.5-2 µg) to adult male Sprague-Dawley rats, the behavior of which was then observed by means of telemetry, open field and elevated plus maze tests. Additionally, plasma concentrations of corticosterone were measured in order to assess the influence of KP-13 on the HPA system. The effects on core temperature were monitored continuously via telemetry. The results demonstrated that KP-13 stimulated the horizontal locomotion (square crossing) in the open field test and decreased the number of entries into and the time spent in the open arms during the elevated plus maze tests.
    [Show full text]
  • The Role of Kisspeptin Neurons in Reproduction and Metabolism
    238 3 Journal of C J L Harter, G S Kavanagh Kisspeptin, reproduction and 238:3 R173–R183 Endocrinology et al. metabolism REVIEW The role of kisspeptin neurons in reproduction and metabolism Campbell J L Harter*, Georgia S Kavanagh* and Jeremy T Smith School of Human Sciences, The University of Western Australia, Perth, Western Australia, Australia Correspondence should be addressed to J T Smith: [email protected] *(C J L Harter and G S Kavanagh contributed equally to this work) Abstract Kisspeptin is a neuropeptide with a critical role in the function of the hypothalamic– Key Words pituitary–gonadal (HPG) axis. Kisspeptin is produced by two major populations of f Kiss1 neurons located in the hypothalamus, the rostral periventricular region of the third f hypothalamus ventricle (RP3V) and arcuate nucleus (ARC). These neurons project to and activate f fertility gonadotrophin-releasing hormone (GnRH) neurons (acting via the kisspeptin receptor, f energy homeostasis Kiss1r) in the hypothalamus and stimulate the secretion of GnRH. Gonadal sex steroids f glucose metabolism stimulate kisspeptin neurons in the RP3V, but inhibit kisspeptin neurons in the ARC, which is the underlying mechanism for positive- and negative feedback respectively, and it is now commonly accepted that the ARC kisspeptin neurons act as the GnRH pulse generator. Due to kisspeptin’s profound effect on the HPG axis, a focus of recent research has been on afferent inputs to kisspeptin neurons and one specific area of interest has been energy balance, which is thought to facilitate effects such as suppressing fertility in those with under- or severe over-nutrition.
    [Show full text]
  • Ligand-Gated Chloride Channels Are Receptors for Biogenic Amines in C
    Ligand-Gated Chloride Channels Are Receptors for Biogenic Amines in C. elegans The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Ringstad, N., N. Abe, and H. R. Horvitz. “Ligand-Gated Chloride Channels Are Receptors for Biogenic Amines in C. elegans.” Science 325, no. 5936 (July 2, 2009): 96-100. As Published http://dx.doi.org/10.1126/science.1169243 Publisher American Association for the Advancement of Science (AAAS) Version Author's final manuscript Citable link http://hdl.handle.net/1721.1/84506 Terms of Use Creative Commons Attribution-Noncommercial-Share Alike 3.0 Detailed Terms http://creativecommons.org/licenses/by-nc-sa/3.0/ NIH Public Access Author Manuscript Science. Author manuscript; available in PMC 2010 October 25. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Science. 2009 July 3; 325(5936): 96±100. doi:10.1126/science.1169243. Ligand-gated chloride channels are receptors for biogenic amines in C. elegans Niels Ringstad1,2, Namiko Abe1,2,3, and H. Robert Horvitz1 1HHMI, Department of Biology and McGovern Institute for Brain Research, MIT, Cambridge MA 02139 Abstract Biogenic amines such as serotonin and dopamine are intercellular signaling molecules that function widely as neurotransmitters and neuromodulators. We have identified in the nematode Caenorhabditis elegans three ligand-gated chloride channels that are receptors for biogenic amines: LGC-53 is a high-affinity dopamine receptor, LGC-55 is a high-affinity tyramine receptor, and LGC-40 is a low-affinity serotonin receptor that is also gated by choline and acetylcholine.
    [Show full text]
  • A Comparative Survey of the RF-Amide Peptide Superfamily
    EDITORIAL published: 10 August 2015 doi: 10.3389/fendo.2015.00120 Editorial: A comparative survey of the RF-amide peptide superfamily Karine Rousseau 1*, Sylvie Dufour 1 and Hubert Vaudry 2 1 Laboratory of Biology of Aquatic Organisms and Ecosystems (BOREA), Muséum National d’Histoire Naturelle, CNRS 7208, IRD 207, Université Pierre and Marie Curie, UCBN, Paris, France, 2 Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982, International Associated Laboratory Samuel de Champlain, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Mont-Saint-Aignan, France Keywords: RF-amide peptides, receptors, evolution, functions, deuterostomes, protostomes The first member of the RF-amide peptide superfamily to be characterized, in 1977, was the cardioexcitatory peptide, FMRFamide, isolated from the ganglia of the clam Macrocallista nimbosa (1). Since then, a large number of such peptides, designated after their C-terminal arginine (R) and amidated phenylalanine (F) residues, have been identified in representative species of all major phyla. The discovery, 12 years ago, that the RF-amide peptide kisspeptin, acting via GPR54, was essential for the onset of puberty and reproduction, has been a major breakthrough in reproductive physiology (2–4). It has also put in front of the spotlights RF-amide peptides and has invigo- rated research on this superfamily of regulatory neuropeptides. The present Research Topic aims at illustrating major advances achieved, through comparative studies in (mammalian and non- mammalian) vertebrates and invertebrates, in the knowledge of RF-amide peptides in terms of evolutionary history and physiological significance. Since 2006, by means of phylogenetic analyses, the superfamily of RFamide peptides has been divided into five families/groups in vertebrates (5, 6): kisspeptin, 26RFa/QRFP, GnIH (including LPXRFa and RFRP), NPFF, and PrRP.
    [Show full text]
  • Serum Levels of Spexin and Kisspeptin Negatively Correlate with Obesity and Insulin Resistance in Women
    Physiol. Res. 67: 45-56, 2018 https://doi.org/10.33549/physiolres.933467 Serum Levels of Spexin and Kisspeptin Negatively Correlate With Obesity and Insulin Resistance in Women P. A. KOŁODZIEJSKI1, E. PRUSZYŃSKA-OSZMAŁEK1, E. KOREK4, M. SASSEK1, D. SZCZEPANKIEWICZ1, P. KACZMAREK1, L. NOGOWSKI1, P. MAĆKOWIAK1, K. W. NOWAK1, H. KRAUSS4, M. Z. STROWSKI2,3 1Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Poznan, Poland, 2Department of Hepatology and Gastroenterology & The Interdisciplinary Centre of Metabolism: Endocrinology, Diabetes and Metabolism, Charité-University Medicine Berlin, Berlin, Germany, 3Department of Internal Medicine, Park-Klinik Weissensee, Berlin, Germany, 4Department of Physiology, Karol Marcinkowski University of Medical Science, Poznan, Poland Received August 18, 2016 Accepted June 19, 2017 On-line November 10, 2017 Summary Corresponding author Spexin (SPX) and kisspeptin (KISS) are novel peptides relevant in P. A. Kolodziejski, Department of Animal Physiology and the context of regulation of metabolism, food intake, puberty and Biochemistry, Poznan University of Life Sciences, Wolynska Street reproduction. Here, we studied changes of serum SPX and KISS 28, 60-637 Poznan, Poland. E-mail: [email protected] levels in female non-obese volunteers (BMI<25 kg/m2) and obese patients (BMI>35 kg/m2). Correlations between SPX or Introduction KISS with BMI, McAuley index, QUICKI, HOMA IR, serum levels of insulin, glucagon, leptin, adiponectin, orexin-A, obestatin, Kisspeptin (KISS) and spexin (SPX) are peptides ghrelin and GLP-1 were assessed. Obese patients had lower SPX involved in regulation of body weight, metabolism and and KISS levels as compared to non-obese volunteers (SPX: sexual functions. In 2014, Kim and coworkers showed that 4.48±0.19 ng/ml vs.
    [Show full text]
  • One-Month of High-Intensity Exercise Did Not Change the Food Intake And
    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/ by-nc-nd/3.0), which permits copy and redistribute the material in any medium or format, provided the original work is properly cited. 8 ENDOCRINE REGULATIONS, Vol. 53, No. 1, 8–13, 2019 doi:10.2478/enr-2019-0002 One-month of high-intensity exercise did not change the food intake and the hypothalamic arcuate nucleus proopiomelanocortin and neuropeptide Y expression levels in male Wistar rats Nazli Khajehnasiri1, Homayoun Khazali2, Farzam Sheikhzadeh3, Mahnaz Ghowsi4 1Department of Biological Sciences, Faculty of Basic Sciences, Higher Education Institute of Rab-Rashid, Tabriz, Iran; 2Department of Animal Sciences and Biotechnology, Faculty of Biological Sciences and Technology, Shahid Beheshti University, Tehran, Iran; 3Department of Animal Sciences, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran; 4Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran E-mail: [email protected] Objective. The hypothalamic arcuate nucleus proopiomelanocortin (POMC) and neuropeptide Y (NPY) circuitries are involved in the inhibition and stimulation of the appetite, respectively. The aim of this study was to investigate the effects of one-month lasting high-intensity exercise on the POMC mRNA and NPY mRNA expression in the above-mentioned brain structure and appetite and food intake levels. Methods. Fourteen male Wistar rats (250±50 g) were used and kept in the well-controlled con- ditions (22±2 °C, 50±5% humidity, and 12 h dark/light cycle) with food and water ad libitum. The rats were divided into two groups (n=7): 1) control group (C, these rats served as controls) and 2) exercised group (RIE, these rats performed a high-intensity exercise for one month (5 days per week) 40 min daily with speed 35 m/min.
    [Show full text]
  • 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.
    [Show full text]
  • CCK-8S) of Protein Phosphorylation in the Neostriatum (Forskonln/N-Methyl-D-Aspartic Acid/Glutamate) GRETCHEN L
    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 11277-11281, December 1993 Neurobiology Regulation by the neuropeptide cholecystokinin (CCK-8S) of protein phosphorylation in the neostriatum (forskonln/N-methyl-D-aspartic acid/glutamate) GRETCHEN L. SNYDER*, GILBERTO FISONE*, PATRIZIA MORINOt, VIDAR GUNDERSEN*, OLE PETTER OTTERSEN*, TOMAS HOKFELTt, AND PAUL GREENGARD*§ *Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021; tDepartment of Histology and Neurobiology, Karolinska Institute, S-10401, Stockholm, Sweden; and *Department of Anatomy, University of Oslo, Blindern, N-0317 Oslo, Norway Contributed by Tomas Hokfelt, August 16, 1993 ABSTRACT Despite physiological evidence that cholecys- rons, apparently through a mechanism that involves the tokinin (CCK) is an excitatory neurotransmitter in the brain, release of an excitatory neurotransmitter and activation of little is known about its mechanism of action. CCK immuno- NMDA receptors. reactivity in the brain, including projections to the striatum, is primarily attributable to the sulfated octapeptide CCK-8S. We report here that CCK-8S abolishes cAMP-dependent phos- MATERIALS AND METHODS phorylation ofa dopamine- and cAMP-regulated 32-kDa phos- Materials. RPMI 1640 balanced salt solution, bovine serum phoprotein (DARPP-32) in striatal neurons. The effect of albumin, and 3-isobutylmethylxanthine were obtained from CCK-8S is prevented by antagonists of CCKB and N-methyl- Sigma; forskolin was from Calbiochem; NMDA and (+)-MK- D-aspartate receptors. Our results support a model in which 801 hydrogen maleate (MK-801) were from Research Bio- CCK-8S, originating from CCK or CCK/glutamate cortico- chemicals; CCK-8S was from Bachem; CI-988 was from J. striatal neurons, promotes the release of an excitatory neuro- Hughes; cAMP, RIA, and ECL Western blotting detection transmitter that causes the dephosphorylation and inactivation kits were from Amersham; and goat anti-mouse horseradish of DARPP-32, a potent protein phosphatase inhibitor, thereby peroxidase-linked antibody was from Pierce.
    [Show full text]
  • An in Vivo Investigation Into the Actions of the Hypothalamic Neuropeptide, QRFP
    An In Vivo Investigation into the Actions of the Hypothalamic Neuropeptide, QRFP A thesis submitted to the University of Manchester for the degree of Doctor of Philosophy in the Faculty of Biology, Medicine and Health Christopher J Cook Faculty of Biology, Medicine and Health School of Medical Sciences 2017 Contents Abstract ........................................................................................................................................... 11 Declaration ........................................................................................................................................ 12 Copyright ........................................................................................................................................... 12 Acknowledgement ............................................................................................................................ 13 Chapter 1 Introduction ................................................................................................. 14 1.1 Energy homeostasis ................................................................................................................ 15 1.2 The control of food intake ...................................................................................................... 16 1.2.1 Peripheral signals regulating food intake .......................................................................... 17 1.2.2 Central aspects of food intake regulation ........................................................................
    [Show full text]
  • The Hypothalamus and the Regulation of Energy Homeostasis: Lifting the Lid on a Black Box
    Proceedings of the Nutrition Society (2000), 59, 385–396 385 CAB59385Signalling39612© NutritionInternationalPNSProceedings Society in body-weight 2000 homeostasisG. of the Nutrition Williams Society et (2000)0029-6651©al.385 Nutrition Society 2000 593 The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box Gareth Williams*, Joanne A. Harrold and David J. Cutler Diabetes and Endocrinology Research Group, Department of Medicine, The University of Liverpool, Liverpool L69 3GA, UK Professor Gareth Williams, fax +44 (0)151 706 5797, email [email protected] The hypothalamus is the focus of many peripheral signals and neural pathways that control energy homeostasis and body weight. Emphasis has moved away from anatomical concepts of ‘feeding’ and ‘satiety’ centres to the specific neurotransmitters that modulate feeding behaviour and energy expenditure. We have chosen three examples to illustrate the physiological roles of hypothalamic neurotransmitters and their potential as targets for the development of new drugs to treat obesity and other nutritional disorders. Neuropeptide Y (NPY) is expressed by neurones of the hypothalamic arcuate nucleus (ARC) that project to important appetite-regulating nuclei, including the paraventricular nucleus (PVN). NPY injected into the PVN is the most potent central appetite stimulant known, and also inhibits thermogenesis; repeated administration rapidly induces obesity. The ARC NPY neurones are stimulated by starvation, probably mediated by falls in circulating leptin and insulin (which both inhibit these neurones), and contribute to the increased hunger in this and other conditions of energy deficit. They therefore act homeostatically to correct negative energy balance. ARC NPY neurones also mediate hyperphagia and obesity in the ob/ob and db/db mice and fa/fa rat, in which leptin inhibition is lost through mutations affecting leptin or its receptor.
    [Show full text]
  • Expression and Localization of Gastrin Messenger RNA and Peptide in Spermatogenic Cells
    Expression and localization of gastrin messenger RNA and peptide in spermatogenic cells. M Schalling, … , T Hökfelt, J F Rehfeld J Clin Invest. 1990;86(2):660-669. https://doi.org/10.1172/JCI114758. Research Article In previous studies we have shown that the gene encoding cholecystokinin (CCK) is expressed in spermatogenic cells of several mammalian species. In the present study we show that a gene homologous to the CCK-related hormone, gastrin, is expressed in the human testis. The mRNA hybridizing to a human gastrin cDNA probe in the human testis was of the same size (0.7 kb) as gastrin mRNA in the human antrum. By in situ hybridization the gastrinlike mRNA was localized to seminiferous tubules. Immunocytochemical staining of human testis revealed gastrinlike peptides in the seminiferous tubules primarily at a position corresponding to spermatids and spermatozoa. In ejaculated spermatozoa gastrinlike immunoreactivity was localized to the acrosome. Acrosomal localization could also be shown in spermatids with electron microscopy. Extracts of the human testis contained significant amounts of progastrin, but no bioactive amidated gastrins. In contrast, ejaculated sperm contained mature carboxyamidated gastrin 34 and gastrin 17. The concentration of gastrin in ejaculated human spermatozoa varied considerably between individuals. We suggest that amidated gastrin (in humans) and CCK (in other mammals) are released during the acrosome reaction and that they may be important for fertilization. Find the latest version: https://jci.me/114758/pdf Expression and Localization of Gastrin Messenger RNA and Peptide in Spermatogenic Cells Martin Schalling,* Hhkan Persson,t Markku Pelto-Huikko,*9 Lars Odum,1I Peter Ekman,I Christer Gottlieb,** Tomas Hokfelt,* and Jens F.
    [Show full text]
  • Dietary Fat Alters the Response of Hypothalamic Neuropeptide Y to Subsequent Energy Intake in Broiler Chickens Xiao J
    © 2017. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2017) 220, 607-614 doi:10.1242/jeb.143792 RESEARCH ARTICLE Dietary fat alters the response of hypothalamic neuropeptide Y to subsequent energy intake in broiler chickens Xiao J. Wang, Shao H. Xu, Lei Liu, Zhi G. Song, Hong C. Jiao and Hai Lin* ABSTRACT Several studies have shown that these hypothalamic neuropeptides Dietary fat affects appetite and appetite-related peptides in birds and are sensitive to body energy status and critical to whole-body mammals; however, the effect of dietary fat on appetite is still unclear metabolic adjustment. NPY reduces energy expenditure by in chickens faced with different energy statuses. Two experiments decreasing adipose tissue thermogenesis (Egawa et al., 1991; Patel were conducted to investigate the effects of dietary fat on food intake et al., 2006; Chao et al., 2011; Zhang et al., 2014). The obesity of and hypothalamic neuropeptides in chickens subjected to two ob/ob mice is attenuated when NPY is knocked out (Erickson et al., fi feeding states or two diets. In Experiment 1, chickens were fed a 1996; Segal-Lieberman et al., 2003). NPY de ciency attenuates high-fat (HF) or low-fat (LF) diet for 35 days, and then subjected to fed responses to a palatable high fat diet in mice (Hollopeter et al., 1998; (HF-fed, LF-fed) or fasted (HF-fasted, LF-fasted) conditions for 24 h. Patel et al., 2006). Animals in which POMC neurons have been In Experiment 2, chickens that were fed a HF or LF diet for 35 days knocked out are obese and hyperphagic (Butler and Cone, 2002; were fasted for 24 h and then re-fed with HF (HF-RHF, LF-RHF) or LF Mencarelli et al., 2012; Diané et al., 2014; Raffan et al., 2016).
    [Show full text]