DOCSLIB.ORG

Reduced Gastrin Releasing Peptide in Cerebrospinal Fluid After Recovery from Bulimia Nervosa

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Reduced Gastrin Releasing Peptide in Cerebrospinal Fluid After Recovery from Bulimia Nervosa Appetite (2001) 37, 9±14 doi:10.1006/appe.2001.0407, available online at http://www.idealibrary.com on 1 Original Article Reduced gastrin releasing peptide in cerebrospinal fluid after recovery from bulimia nervosa G.K. Franka,W.H. Kaye a, E.E. Ladenheimb and C. McConahaa aSchoolof Medicine, Department of Psychiatry,Western Psychiatric Institute and Clinic,University of Pittsburgh; bSchoolof Medicine, Department of Psychiatryand Behavioral Sciences,The Johns Hopkins University,Baltimore (Received 20 September 2000, revision11April 2001,accepted in revised form 20 April 2001) People with anorexia (AN) and bulimia nervosa (BN) have altered patterns of eating. It is possible that alterations of the neuropeptide gastrin releasing peptide (GRP), a bombesin (BBS) -like peptide with potent central anorexigenic activity, could contribute to disturbed eating behavior. To avoid the confounding effects of pathologic eating behavior, we measured cerebrospinal fluid (CSF) GRP concentrations in women who were long-term recovered ( >1 year, normal weight, and regular menstrual cycles, no bingeing or purging) from AN (REC AN, N 12) or BN (REC BN, N 21) compared to healthy control women (NC, N 15). CSF GRP was significantly lower (2 9Á41(3), p < 0Á01) in REC BN (9Á6 Æ 3Á1 pg/ml) compared to NC (13Á4 Æ 5Á5 pg/ml) and REC AN (11Á6 Æ 2Á9 pg/ ml). Persistent GRP abnormalities after recovery from BN raise the possibility that this alteration might be trait- related and contribute to episodic hyperphagia in BN. # 2001 Academic Press Introduction of food restriction alternating with regular binge-purge episodes. The etiology of EDs is not known (American The eating disorders (EDs) anorexia (AN) and bulimia Psychiatric Association, 1994). Recent studies suggest nervosa (BN) are characterized by disturbed eating that EDs are familial and that a genetic predisposition behaviors and comorbid disturbances of mood, impulse might contribute to their etiology (Lilenfeld et al., 1998; control, and temperament. Women with AN show a Strober et al., 2000). pattern of food restriction and emaciation; however, A number of neuropeptides contribute to the modu- some AN are pure food restrictors, whereas others also lation of appetite regulation (Kalra et al., 1999). It is show binge-purging type behaviors. Women with BN are theoretically possible that a disturbance of the modu- usually at a normal body weight, and engage in a pattern lation of one or more neuropeptide systems plays a role in disturbed eating behavior in humans. One neuro- peptide system of interest is human gastrin releasing Supported in part by grants from NIMH #2 R01 MH peptide (GRP). GRP is a 27 amino acid peptide that 42984-09 ``The Neurobiology of Feeding Behavior in shares a similar decapeptide with bombesin (BBS; Bulimia''; Children's Hospital Clinical Research Center, Pittsburgh, PA (#5M01 RR00084), and NIMH #2 R01 Brown et al., 1980), and belongs to the family of MH 46001-07A1 ``Serotonin: A Trait Disturbance in ``bombesin-like peptides.'' BBS was first isolated from Anorexia Nervosa''. amphibian skin (Anastasi et al., 1971) and showed Address correspondence to: Walter H. Kaye, M.D., anorexigenic effects when administered peripherally or University of Pittsburgh, Western Psychiatric Institute and centrally in mammals (Gibbs and Smith, 1988). GRP is Clinic, Room E-724, 3811 O'Hara Street, Pittsburgh, PA 15213, U. S. A. Fax: 1 412 624 6618. not as potent as BBS, but otherwise has similar Email: [email protected] effects (Morley et al., 1985). Peripheral and central 0195±6663/01/040009+06 $35.00/0 # 2001 Academic Press 10 G. K. Frank et al. administration of GRP attenuates food intake in menstrual cycles; have not binged, purged (i.e. not mammals and humans (Bray 1995; Flynn, 1994). Per- engaged in self-induced vomiting, the use of laxatives ipherally, BBS-like receptors are distributed throughout or diuretics), excessively exercised, or engaged in the gastrointestinal (GI) tract, with receptors that have restrictive eating patterns; and have not met criteria specifically high affinity for GRP (von Schrenck et al., for substance-use related disorders. Subjects were free 1990). They take part in the regulation of GI hormone of medication for 6 weeks prior to the study and gave and enzyme secretion, cell growth, smooth muscle informed consent. The control women (NC) had no activity and blood glucose levels (Dietrich, 1994; Walsh history of an eating disorder or any psychiatric, et al., 1981). In the central nervous system (CNS), dis- medical, or neurologic illness. They had normal tinct BBS-like receptor subtypes have been identified in menstrual cycles, and had been within a normal weight brain tissue such as the bed nucleus of the stria termi- range since menarche. They also had no first degree nalis, the olfactory tubercle, the putamen and neocortex, relatives with an eating disorder. Methods and with a neuromedin B and a GRP preferring subtype psychological assessment data are described in detail (Ladenheim et al., 1992; Wolf & Moody, 1985). Both elsewhere (Kaye et al., 1998a, 1999). For many of the subtypes have been implicated in the modulation of subjects, CSF 5-hydroxyindole acetic acid had been BBS-like peptide induced food suppression (Ladenheim measured previously. et al., 1996). In addition, central GRP also modulates A lumbar puncture (LP) for obtaining CSF samples temperature regulation and grooming behavior in ani- was performed during the first 10 days of the follicular mals (Cowan, 1988). Disturbances of neuropeptides phase of the menstrual cycle. Subjects were admitted to a could be a consequence of disturbed eating behavior or research laboratory on the Eating Disorders Unit of malnutrition, or pre-morbid traits that contribute to a Western Psychiatric Institute and Clinic at 9 a.m. on the vulnerability to develop an ED. Determining whether day prior to the LP for adaptation to the laboratory and abnormalities are a consequence or a potential ante- for psychological assessments. Subjects fasted over- cedent of pathological feeding behavior is a major night, and the LP was performed the next day between 9 question in the study of eating disorders. It is impractical a.m. and 9:30 a.m. LP samples were frozen in liquid to study people with ED prospectively due to the young nitrogen and stored at 80C. For the GRP assay a age of onset and difficulty in pre-morbid identification commercial kit for radio immuno assay (RAI) from of people who will develop an ED. Therefore, we deci- Peninsula Laboratories, Inc., San Carlos, CA, was used. ded to study women who had recovered for more than a The antibody in that kit shows 100% cross reactivity year from AN or BN. Any persistent psychobiological with human GRP, as well as with BBS. No cross reac- abnormalities might be trait-related and potentially tivity is reported for human gastrin I, human big gastrin- have contributed to the pathogenesis of this disorder. In 1 peptide, gastric inhibitory peptide, or substance P. The this study we measured cerebrospinal fluid (CSF) values variability of the assay between runs was 4 Æ 3% of human GRP, a human BBS-like peptide. We hypo- (mean Æ SD). Plasma -hydroxybutyrate (BHBA), a thesized that AN would have increased and BN ketone body, was assessed as an index of starvation. decreased CSF values of GRP. BHBA was measured by the enzymatic method of Williamson et al. (1962). Statistical analyses were performed using the SPSS software package (SPSS, Chicago, IL; Barcikowski Materials and methods 1984). Data exploration assessed whether data were normally distributed (Shapiro-Wilk test). When the Thirty-three women who had previously met DSM-IV assumption of normality was met, One-Way ANOVA criteria for an ED were recruited: 21 women recovered assessed whether group means were similar, and from normal weight BN (REC BN), and 12 subjects Scheffe's post hoc tests compared individual group dif- recovered from binge eating/purging (eight) or restrict- ferences. All variables aside from age and CSF GRP ing type (four) AN (REC AN). The REC BN women were normally distributed. When the assumption of had never had AN. Recovered ED subjects were normality was not met, Kruskal-Wallis test assessed compared to 15 female normal controls (NC), who three group comparisons, and Mann-Whitney U tests were recruited through advertisements in local news- assessed individual group differences. Correlations were papers and who were without lifetime psychiatric or investigated using Pearson Correlations for normally major medical illnesses. In the year before the study, all distributed and Spearman Correlation Coefficients for participating recovered subjects had to maintain a non-normally distributed variables. All data are body weight of > 90% average body weight (ABW; expressed as mean Æ standard deviation (SD). Group Metropolitan Life Insurance, 1959); have regular differences were considered significant if p < 0Á05. Gastrin releasing peptide and bulimia nervosa 11 Results compared with REC AN. Lifetime high % ABW was higher in REC BN compared with NC and REC AN. Age was similar between groups (Table 1). However, Lifetime low % ABW was lower in REC AN % ABW at the time of the study was higher in REC compared with NC and REC BN. BHBA was similar BN compared with NC and REC AN, and in NC between groups. There was no difference between length of recovery between groups. One CSF GRP value for the NC group was excluded 35 as a non-true outlier (195 pg/ml). There was a significant difference between group CSF GRP levels (Table 1). Figure 1 shows a scatterplot with the distribution of the GRP values across groups. The CSF GRP in REC BN 30 showed some overlap in distribution with NC and AN. However, the majority of CSF GRP data points in REC BN women was below 10 pmol/ml (15/21), whereas the majority of data points for NC (12/15) and REC AN (9/ 25 12) was above 10 pmol/ml.
Load more

Recommended publications
  • 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]
  • Rfamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential
    Pharmaceuticals 2011, 4, 1248-1280; doi:10.3390/ph4091248 OPEN ACCESS Pharmaceuticals ISSN 1424-8247 www.mdpi.com/journal/pharmaceuticals Review RFamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential Maria Findeisen †, Daniel Rathmann † and Annette G. Beck-Sickinger * Institute of Biochemistry, Leipzig University, Brüderstraße 34, 04103 Leipzig, Germany; E-Mails: [email protected] (M.F.); [email protected] (D.R.) † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +49-341-9736900; Fax: +49-341-9736909. Received: 29 August 2011; in revised form: 9 September 2011 / Accepted: 15 September 2011 / Published: 21 September 2011 Abstract: Different neuropeptides, all containing a common carboxy-terminal RFamide sequence, have been characterized as ligands of the RFamide peptide receptor family. Currently, five subgroups have been characterized with respect to their N-terminal sequence and hence cover a wide pattern of biological functions, like important neuroendocrine, behavioral, sensory and automatic functions. The RFamide peptide receptor family represents a multiligand/multireceptor system, as many ligands are recognized by several GPCR subtypes within one family. Multireceptor systems are often susceptible to cross-reactions, as their numerous ligands are frequently closely related. In this review we focus on recent results in the field of structure-activity studies as well as mutational exploration of crucial positions within this GPCR system. The review summarizes the reported peptide analogs and recently developed small molecule ligands (agonists and antagonists) to highlight the current understanding of the pharmacophoric elements, required for affinity and activity at the receptor family.
    [Show full text]
  • Co-Regulation of Hormone Receptors, Neuropeptides, and Steroidogenic Enzymes 2 Across the Vertebrate Social Behavior Network 3 4 Brent M
    bioRxiv preprint doi: https://doi.org/10.1101/435024; this version posted October 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Co-regulation of hormone receptors, neuropeptides, and steroidogenic enzymes 2 across the vertebrate social behavior network 3 4 Brent M. Horton1, T. Brandt Ryder2, Ignacio T. Moore3, Christopher N. 5 Balakrishnan4,* 6 1Millersville University, Department of Biology 7 2Smithsonian Conservation Biology Institute, Migratory Bird Center 8 3Virginia Tech, Department of Biological Sciences 9 4East Carolina University, Department of Biology 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 1 bioRxiv preprint doi: https://doi.org/10.1101/435024; this version posted October 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Running Title: Gene expression in the social behavior network 2 Keywords: dominance, systems biology, songbird, territoriality, genome 3 Corresponding Author: 4 Christopher Balakrishnan 5 East Carolina University 6 Department of Biology 7 Howell Science Complex 8 Greenville, NC, USA 27858 9 [email protected] 10 2 bioRxiv preprint doi: https://doi.org/10.1101/435024; this version posted October 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Five Decades of Research on Opioid Peptides: Current Knowledge and Unanswered Questions
    Molecular Pharmacology Fast Forward. Published on June 2, 2020 as DOI: 10.1124/mol.120.119388 This article has not been copyedited and formatted. The final version may differ from this version. File name: Opioid peptides v45 Date: 5/28/20 Review for Mol Pharm Special Issue celebrating 50 years of INRC Five decades of research on opioid peptides: Current knowledge and unanswered questions Lloyd D. Fricker1, Elyssa B. Margolis2, Ivone Gomes3, Lakshmi A. Devi3 1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; E-mail: [email protected] 2Department of Neurology, UCSF Weill Institute for Neurosciences, 675 Nelson Rising Lane, San Francisco, CA 94143, USA; E-mail: [email protected] 3Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, Annenberg Downloaded from Building, One Gustave L. Levy Place, New York, NY 10029, USA; E-mail: [email protected] Running Title: Opioid peptides molpharm.aspetjournals.org Contact info for corresponding author(s): Lloyd Fricker, Ph.D. Department of Molecular Pharmacology Albert Einstein College of Medicine 1300 Morris Park Ave Bronx, NY 10461 Office: 718-430-4225 FAX: 718-430-8922 at ASPET Journals on October 1, 2021 Email: [email protected] Footnotes: The writing of the manuscript was funded in part by NIH grants DA008863 and NS026880 (to LAD) and AA026609 (to EBM). List of nonstandard abbreviations: ACTH Adrenocorticotrophic hormone AgRP Agouti-related peptide (AgRP) α-MSH Alpha-melanocyte stimulating hormone CART Cocaine- and amphetamine-regulated transcript CLIP Corticotropin-like intermediate lobe peptide DAMGO D-Ala2, N-MePhe4, Gly-ol]-enkephalin DOR Delta opioid receptor DPDPE [D-Pen2,D- Pen5]-enkephalin KOR Kappa opioid receptor MOR Mu opioid receptor PDYN Prodynorphin PENK Proenkephalin PET Positron-emission tomography PNOC Pronociceptin POMC Proopiomelanocortin 1 Molecular Pharmacology Fast Forward.
    [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]
  • REVIEW the Role of Rfamide Peptides in Feeding
    3 REVIEW The role of RFamide peptides in feeding David A Bechtold and Simon M Luckman Faculty of Life Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK (Requests for offprints should be addressed to D A Bechtold; Email: [email protected]) Abstract In the three decades since FMRFamide was isolated from the evolution. Even so, questions remain as to whether feeding- clam Macrocallista nimbosa, the list of RFamide peptides has related actions represent a primary function of the RFamides, been steadily growing. These peptides occur widely across the especially within mammals. However, as we will discuss here, animal kingdom, including five groups of RFamide peptides the study of RFamide function is rapidly expanding and with identified in mammals. Although there is tremendous it so is our understanding of how these peptides can influence diversity in structure and biological activity in the RFamides, food intake directly as well as related aspects of feeding the involvement of these peptides in the regulation of energy behaviour and energy expenditure. balance and feeding behaviour appears consistently through Journal of Endocrinology (2007) 192, 3–15 Introduction co-localised with classical neurotransmitters, including acetyl- choline, serotonin and gamma-amino bulyric acid (GABA). The first recognised member of the RFamide neuropeptide Although a role for RFamides in feeding behaviour was family was the cardioexcitatory peptide, FMRFamide, first suggested over 20 years ago, when FMRFamide was isolated from ganglia of the clam Macrocallista nimbosa (Price shown to be anorexigenic in mice (Kavaliers et al. 1985), the & Greenberg 1977). Since then a large number of these question of whether regulating food intake represents a peptides, defined by their carboxy-terminal arginine (R) and primary function of RFamide signalling remains.
    [Show full text]
  • Central Nervous System and Peripheral Effects of ACTH, MSH, and Related Neuropeptides
    Peptides, Vol. 3, pp. 411--420, 1982. Printed in the U.S.A. Central Nervous System and Peripheral Effects of ACTH, MSH, and Related Neuropeptides BILL E. BECKWITH 1 Department of Psychology, University of North Dakota, Grand Forks, ND 58202 AND CURT A. SANDMAN Department of Psychiatry and Human Behavior, Department of Psychobiology University of California at Irvine, Irvine, CA and Fairview State Hospital, Costa Mesa, CA 92626 BECKWITH, B. E. AND C. A. SANDMAN. Central nervous system and peripheral effects of ACTH, MSH, and related neuropeptides. PEPTIDES 3(3) 411--420, 1982.--Adrenocorticotropic Hormone (ACTH), Melanocyte-Stimulating Hor- mone (MSH), and related peptides have been shown to have several neurogenic effects: alteration of cerebral protein synthesis, RNA synthesis, protein phosphorylation, and neurotransmitter turnover. Furthermore, there appears to be an ACTH containing circuit in the CNS which originates in the arcuate nucleus. Changes in concentration of the peptides in this family have been shown to alter electrophysiology, neuromuscular function, and behavior (e.g., grooming, learning) in infrahuman subjects. These findings suggest that the neuropeptides MSH and ACTH influence the capacity of an organism to efficiently evaluate information and influence the affective functioning of humans. ACTH Affect Attention Depression Electrophysiology MSH Neuropeptides ADRENOCORTICOTROPIC hormone (ACTH) is a linear nology also was stimulated by at least two main bodies of nonatriacontapeptide, i.e. a peptide consisting of 39 amino findings: (1) The discovery of pituitary hormones in the brain acid residues, which can be derived from a larger 31,000 and (2) the discovery of behavioral altering consequences of dalton glycoprotein [77] and is but one member of a chemi- these hormones and their fragments and analogues (see re- cally and biogenetically related family of polypeptides which views [6, 1 l, 65]).
    [Show full text]
  • Orexin a Promotes Histamine, but Not Norepinephrine Or Serotonin, Re- Lease in Frontal Cortex of Mice1
    Http://www.chinaphar.comActa Pharmacologica Sinica 2005 Feb; 26 (2): 155–159 Hong ZY et al Full-length article Orexin A promotes histamine, but not norepinephrine or serotonin, re- lease in frontal cortex of mice1 Zong-yuan HONG2,3, Zhi-li HUANG3,4,5, Wei-min QU3, Naomi EGUCHI3 2School of Life Science, University of Science and Technology of China, Hefei 230027, China; 3Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Furuedai, Suita, Osaka 565-0874, Japan; 4Department of Pharmacology, Shanghai Medical College of Fudan University, Shanghai 200032, China Key words Abstract orexin A; histamine; noradrenaline; sero- Aim: To investigate the effects of orexin A on release of histamine, norepinephrine, tonin; microdialysis; frontal cortex and serotonin in the frontal cortex of mice. Methods: Samples for measuring 1 Project supported in part by a grant-in-aid histamine, norepinephrine, and serotonin contents were collected by in vivo for scientific research from the Japan microdialysis of the frontal cortex of anesthetized mice. The histamine, Society for the Promotion of Science (ZLH) noradrenaline, and serotonin content in dialysates were measured by HPLC and Osaka City. 5 Correspondence to Zhi-li HUANG, MD, PhD. techniques. Results: Intracrebroventricular injection of orexin A at doses of 12.5, Phn 81-6-6872-4851. 50, and 200 pmol per mouse promoted histamine release from the frontal cortex in Fax 81-6-6872-2841. a dose-dependent manner. At the highest dose given, 200 pmol, orexin A signifi- E-mail [email protected] cantly induced histamine release, with the maximal magnitude being 230% over Received 2004-09-13 the mean basal release.
    [Show full text]
  • Growing up POMC: Pro-Opiomelanocortin in the Developing Brain
    Growing Up POMC: Pro-opiomelanocortin in the Developing Brain Stephanie Louise Padilla Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2011 © 2011 Stephanie Louise Padilla All Rights Reserved ABSTRACT Growing Up POMC: Pro-opiomelanocortin in the Developing Brain Stephanie Louise Padilla Neurons in the arcuate nucleus of the hypothalamus (ARH) play a central role in the regulation of body weight and energy homeostasis. ARH neurons directly sense nutrient and hormonal signals of energy availability from the periphery and relay this information to secondary nuclei targets, where signals of energy status are integrated to regulate behaviors related to food intake and energy expenditure. Transduction of signals related to energy status by Pro-opiomelanocortin (POMC) and neuropeptide-Y/agouti-related protein (NPY/AgRP) neurons in the ARH exert opposing influences on secondary neurons in central circuits regulating energy balance. My thesis research focused on the developmental events regulating the differentiation and specification of cell fates in the ARH. My first project was designed to characterize the ontogeny of Pomc- and Npy-expressing neurons in the developing mediobasal hypothalamus (Chapter 2). These experiments led to the unexpected finding that during mid-gestation, Pomc is broadly expressed in the majority of newly-born ARH neurons, but is subsequently down-regulated during later stages of development as cells acquire a terminal cell identity. Moreover, these studies demonstrated that most immature Pomc-expressing progenitors subsequently differentiate into non-POMC neurons, including a subset of functionally distinct NPY/AgRP neurons.
    [Show full text]
  • 60 YEARS of POMC: Biosynthesis, Trafficking, and Secretion of Pro
    56:4 N X CAWLEY and others Biosynthesis of POMC-derived 56:4 T77–T97 Thematic Review peptides 60 YEARS OF POMC Biosynthesis, trafficking, and secretion of pro-opiomelanocortin-derived peptides Correspondence should be addressed Niamh X Cawley, Zhaojin Li and Y Peng Loh to Y Peng Loh Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Email Development, National Institutes of Health, Bethesda, Maryland, USA [email protected] Abstract Pro-opiomelanocortin (POMC) is a prohormone that encodes multiple smaller peptide Key Words hormones within its structure. These peptide hormones can be generated by cleavage f hypothalamus- of POMC at basic residue cleavage sites by prohormone-converting enzymes in the pituitary-adrenal axis regulated secretory pathway (RSP) of POMC-synthesizing endocrine cells and neurons. f POMC sorting The peptides are stored inside the cells in dense-core secretory granules until released f POMC-derived peptide secretion in a stimulus-dependent manner. The complexity of the regulation of the biosynthesis, f vesicle trafficking trafficking, and secretion of POMC and its peptides reflects an impressive level of f prohormone control over many factors involved in the ultimate role of POMC-expressing cells, that processing enzymes is, to produce a range of different biologically active peptide hormones ready for action when signaled by the body. From the discovery of POMC as the precursor to adrenocorticotropic hormone (ACTH) and β-lipotropin in the late 1970s to our current Journal of Molecular Endocrinology knowledge, the understanding of POMC physiology remains a monumental body of work that has provided insight into many aspects of molecular endocrinology.
    [Show full text]
  • Views of the NIDA, NINDS Or the National Summed Across the Three Auditory Forebrain Lobule Sec- Institutes of Health
    Xie et al. BMC Biology 2010, 8:28 http://www.biomedcentral.com/1741-7007/8/28 RESEARCH ARTICLE Open Access The zebra finch neuropeptidome: prediction, detection and expression Fang Xie1, Sarah E London2,6, Bruce R Southey1,3, Suresh P Annangudi1,6, Andinet Amare1, Sandra L Rodriguez-Zas2,3,5, David F Clayton2,4,5,6, Jonathan V Sweedler1,2,5,6* Abstract Background: Among songbirds, the zebra finch (Taeniopygia guttata) is an excellent model system for investigating the neural mechanisms underlying complex behaviours such as vocal communication, learning and social interactions. Neuropeptides and peptide hormones are cell-to-cell signalling molecules known to mediate similar behaviours in other animals. However, in the zebra finch, this information is limited. With the newly-released zebra finch genome as a foundation, we combined bioinformatics, mass-spectrometry (MS)-enabled peptidomics and molecular techniques to identify the complete suite of neuropeptide prohormones and final peptide products and their distributions. Results: Complementary bioinformatic resources were integrated to survey the zebra finch genome, identifying 70 putative prohormones. Ninety peptides derived from 24 predicted prohormones were characterized using several MS platforms; tandem MS confirmed a majority of the sequences. Most of the peptides described here were not known in the zebra finch or other avian species, although homologous prohormones exist in the chicken genome. Among the zebra finch peptides discovered were several unique vasoactive intestinal and adenylate cyclase activating polypeptide 1 peptides created by cleavage at sites previously unreported in mammalian prohormones. MS-based profiling of brain areas required for singing detected 13 peptides within one brain nucleus, HVC; in situ hybridization detected 13 of the 15 prohormone genes examined within at least one major song control nucleus.
    [Show full text]
  • Evolutionarily Conserved TRH Neuropeptide Pathway Regulates
    Evolutionarily conserved TRH neuropeptide pathway PNAS PLUS regulates growth in Caenorhabditis elegans Elien Van Sinaya, Olivier Mirabeaub, Geert Depuydta, Matthias Boris Van Hiela, Katleen Peymena, Jan Watteynea, Sven Zelsa, Liliane Schoofsa,1, and Isabel Beetsa,1 aFunctional Genomics and Proteomics Group, Department of Biology, KU Leuven, 3000 Leuven, Belgium; and bGenetics and Biology of Cancers Unit, Institut Curie, INSERM U830, Paris Sciences et Lettres Research University, Paris 75005, France Edited by Iva Greenwald, Columbia University, New York, NY, and approved April 7, 2017 (received for review October 20, 2016) In vertebrates thyrotropin-releasing hormone (TRH) is a highly con- THs likely originated early in deuterostomian evolution (15), the served neuropeptide that exerts the hormonal control of thyroid- prime role of TRH in controlling TH levels seems to have evolved stimulating hormone (TSH) levels as well as neuromodulatory more recently in vertebrates. In fish and amphibians, TRH has no or functions. However, a functional equivalent in protostomian ani- only a minor effect on the production of TSH but allows the secretion mals remains unknown, although TRH receptors are conserved in of growth hormone (GH), prolactin (PRL), and α-melanocyte– proto- and deuterostomians. Here we identify a TRH-like neuropep- stimulating hormone (α-MSH) (9, 16). In nonmammalian vertebrates tide precursor in Caenorhabditis elegans that belongs to a bilaterian corticotropin-releasing hormone (CRH), a prime regulator of stress family of TRH precursors. Using CRISPR/Cas9 and RNAi reverse genetics, responses, is a potent inducer of TSH secretion (16). These effects we show that TRH-like neuropeptides, through the activation of their raise the question as to what the ancient function of TRH might have receptor TRHR-1, promote growth in C.
    [Show full text]