DOCSLIB.ORG

Chronic Central Infusion of Ghrelin Increases Hypothalamic

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chronic Central Infusion of Ghrelin Increases Hypothalamic Chronic Central Infusion of Ghrelin Increases Hypothalamic Neuropeptide Y and Agouti-Related Protein mRNA Levels and Body Weight in Rats Jun Kamegai, Hideki Tamura, Takako Shimizu, Shinya Ishii, Hitoshi Sugihara, and Ichiji Wakabayashi Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was originally puri- fied from the rat stomach. Like the synthetic growth nergy intake and expenditure are tightly regu- hormone secretagogues (GHSs), ghrelin specifically re- lated in mammals (1). Several neuronal popula- leases growth hormone (GH) after intravenous admin- tions, particularly in the hypothalamic arcuate istration. Also consistent with the central actions of nucleus (ARC), are involved in the regulation of GHSs, ghrelin-immunoreactive cells were shown to be E energy homeostasis and have been implicated as possi- located in the hypothalamic arcuate nucleus as well as the stomach. Recently, we showed that a single central ble targets of orexigenic peptides (1). These include administration of ghrelin increased food intake and neuropeptide Y (NPY)/agouti-related protein (AGRP) co- hypothalamic agouti-related protein (AGRP) gene ex- expressing neurons, pro-opiomelanocortin (POMC) neu- pression in rodents, and the orexigenic effect of this rons, and growth hormone–releasing hormone (GHRH) peptide seems to be independent of its GH-releasing neurons, which are known to be stimulated (NPY and activity. However, the effect of chronic infusion of AGRP) or suppressed (POMC and GHRH) by starvation ghrelin on food consumption and body weight and their (2–10). However, central administration of NPY, AGRP, possible mechanisms have not been elucidated. In this and GHRH increased food intake in rats, whereas ␣-mela- study, we determined the effects of chronic intracere- ␣ broventricular treatment with ghrelin on metabolic fac- nocyte–stimulating hormone ( -MSH), an end product of tors and on neuropeptide genes that are expressed in POMC processing, decreased food intake when injected hypothalamic neurons that have been previously shown centrally (11–13). to express the GHS-R and to regulate food consumption. The growth hormone secretagogues (GHSs) are syn- Chronic central administration of rat ghrelin (1 ␮g/rat thetic peptide and nonpeptide compounds that stimulate every 12 h for 72 h) significantly increased food intake the pulsatile release of growth hormone (GH) after intra- and body weight. However, it did not affect plasma venous administration (14). Central administration of insulin, glucose, leptin, or GH concentrations. We also GHSs also stimulates feeding behavior (15). GHS receptor found that chronic central administration of ghrelin increased both neuropeptide Y (NPY) mRNA levels (GHS-R) mRNA is expressed in the pituitary gland and in of saline-treated controls; P < 0.05) and several areas of the brain, including the hypothalamus 10.1% ؎ 151.0) AGRP mRNA levels (160.0 ؎ 22.5% of saline-treated (16). In the hypothalamus, GHS-R mRNA is expressed in controls; P < 0.05) in the arcuate nucleus. Thus, the NPY/AGRP-, POMC-, and GHRH-containing neurons (17– primary hypothalamic targets of ghrelin are NPY/AGRP- 19). Ghrelin, an endogenous ligand for the GHS-R, was containing neurons, and ghrelin is a newly discovered purified from the rat stomach (20). Similar to the synthetic orexigenic peptide in the brain and stomach. Diabetes GHSs, ghrelin specifically releases GH after intravenous 50:2438–2443, 2001 administration. Recently, we showed that a single central administration of ghrelin increased food intake and hypo- thalamic AGRP gene expression in rodents, and the orexi- genic effect of this peptide seems to be independent of its GH-releasing activity (21). Thus, ghrelin has an alternative role in stimulating food intake in addition to releasing GH from the pituitary. It has been reported that previous exposure to GHS can induce desensitization of the subse- quent GH responses to GHS, indicating that homologous From the Department of Medicine, Nippon Medical School, Tokyo, Japan. desensitization is observed after continuous exposure to Address correspondence and reprint requests to Jun Kamegai, Department GHS with respect to GH release (22,23). However, the of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113- 8603, Japan. E-mail: [email protected]. effect of chronic infusion of ghrelin on food consumption Received for publication 1 December 2000 and accepted in revised form 31 and body weight and their possible mechanisms has not July 2001. AGRP, agouti-related protein; ARC, hypothalamic arcuate nucleus; GH, been elucidated. In this study, we determined the effects of growth hormone; GHRH, growth hormone–releasing hormone; GHS, growth chronic intracerebroventricular treatment with ghrelin on hormone secretagogue; GHS-R, growth hormone secretagogue receptor; metabolic factors and on the hypothalamic NPY, AGRP, ␣-MSH, ␣-melanocyte–stimulating hormone; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; RIA, radioimmunoassay; SS, somatostatin; SSC, saline POMC, and GHRH mRNA levels using radioactive in situ sodium citrate. hybridization histochemistry. 2438 DIABETES, VOL. 50, NOVEMBER 2001 J. KAMEGAI AND ASSOCIATES RESEARCH DESIGN AND METHODS TABLE 1 Animals. Male Sprague-Dawley rats (250–280 g) were housed in air-condi- Comparisons of food intake, body weight, fat weight, plasma tioned animal quarters, with lights on between 08:00 and 20:00 h, and were glucose, insulin, leptin, and GH in rats treated with rat ghrelin or given food and water ad libitum. The animals were anesthetized with ether, saline for 3 days and a 23-gauge stainless-steel cannula was implanted into the right lateral ventricle using a stereotaxic apparatus, as previously described (24). The Control Ghrelin-treated upper incisor bar was set 3.3 mm below the interauricular line, and the bregma was taken as A-P zero. The cannula tip was placed at A Ϫ0.9, L Ϫ1.2, and V n 55 Ϫ3.6 mm and secured in place with dental acrylic. Only those rats whose Food intake (g/72 h) 97.8 Ϯ 4.5 116.0 Ϯ 6.2* cerebrospinal fluid overflowed through the cannula were used for the exper- Initial body weight (g) 373 Ϯ 12 379 Ϯ 13 iment. They were kept in individual cages and habituated by handling every Final body weight (g) 376 Ϯ 14 391 Ϯ 15 day. Injections of the peptide were performed 14 days after placement of the ⌬ Body weight (g) 2.8 Ϯ 2.5 11.8 Ϯ 2.9* cannula. Experiments were conducted according to the principles and proce- Epididymal fat weight (g) 3.6 Ϯ 0.3 3.9 Ϯ 0.3 dures outlined in the National Institutes of Health Guide for the Care and Use Retroperitoneal fat weight (g) 3.2 Ϯ 0.4 4.2 Ϯ 0.4 of Laboratory Animals. Ϯ Ϯ Experimental protocol. Rat ghrelin (1 ␮g/rat; provided by Dr. K. Kangawa, Inguinal fat weight (g) 3.8 0.3 4.0 0.2 National Cardiovascular Center Research Institute, Osaka, Japan) or saline Plasma glucose (mg/dl) 144.8 Ϯ 3.2 148.6 Ϯ 5.1 was injected every 12 h for 72 h. Food intake and body weights were measured Plasma insulin (ng/ml) 4.56 Ϯ 0.43 4.90 Ϯ 0.28 daily. Animals were anesthetized with pentobarbital (70 mg/kg i.p.) ϳ4 h after Plasma leptin (ng/ml) 5.65 Ϯ 1.39 6.99 Ϯ 0.83 the final injection of ghrelin. The blood was collected, and plasma was Plasma GH (ng/ml) 8.61 Ϯ 3.18 6.45 Ϯ 1.38 separated by centrifugation and stored at Ϫ70°C until assay. Plasma glucose was measured by the glucose oxidase method. Plasma insulin and leptin were Data are means Ϯ SD. *P Ͻ 0.05 compared with the control group. measured by radioimmunoassay (RIA) using a commercially available rat insulin RIA kit (Amersham, Tokyo) and rat leptin RIA kit (Linco Research, St. Charles, MO), respectively. GH levels were measured with a double-antibody 6.2 g for ghrelin vs. 97.8 Ϯ 4.5 g for saline; n ϭ 5 rats per RIA using materials supplied by the National Institute of Diabetes and group; P Ͻ 0.05) (Table 1) and body weight (11.8 Ϯ 2.9 g Digestive and Kidney Diseases, National Institutes of Health (Bethesda, MD), for ghrelin vs. 2.8 Ϯ 2.5 g for saline; n ϭ 5 rats per group; as previously described (21). Epididymal, retroperitoneal, and inguinal fat Ͻ pads were dissected and weighed. Anesthetized rats were perfused with 2% P 0.05 (Table 1), as compared with intracerebroventric- paraformaldehyde, and the brain was kept overnight at 4°C in the same ular injection of the vehicle. However, it did not affect the fixative containing 20% sucrose. weight of three fat deposits or of plasma insulin, glucose, In situ hybridization. Frozen coronal sections, 30 ␮m thick, were cut with leptin, and GH concentrations, although there was the a cryostat, mounted onto Silan-coated slides (Shin-Etsu Chemical, Tokyo), and air-dried. The medial basal hypothalamus from the rostral end of the third trend toward higher levels of fat pad weights and plasma ventricle to the caudal end of the ARC was processed for in situ hybridization leptin and insulin levels in the ghrelin-treated group (Table using 35S-labeled riboprobes for NPY, AGRP, POMC, and GHRH mRNA, as 1). previously described (21). The hybridization protocol has been described Hypothalamic neuropeptide gene expressions. Cen- previously (25). In brief, sections were dried, digested by proteinase K (10 tral administration of ghrelin increased the levels of NPY ␮g/ml), and acetylated with 0.25% acetic anhydride. Sections were rinsed Ϯ brieflyin2ϫ saline sodium citrate (SSC) and then air-dried. The probe was mRNA in the ARC to 151.0 10.1% of the saline-treated dissolved in hybridization buffer (10 mmol/l Tris [pH 8.0], containing 50% controls (n ϭ 5 rats per group; P Ͻ 0.05) (Fig.
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]
  • Interactions of the Growth Hormone Secretory Axis and the Central Melanocortin System
    INTERACTIONS OF THE GROWTH HORMONE SECRETORY AXIS AND THE CENTRAL MELANOCORTIN SYSTEM By AMANDA MARIE SHAW A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2004 Copyright 2004 by Amanda Marie Shaw This document is dedicated to my wonderful family. ACKNOWLEDGMENTS I would like to thank a number of people who greatly helped me through this long process of earning my Ph.D. First, I would like to thank my husband, Jason Shaw for his unwavering love and support during this time. I would also like to thank my parents, Robert and Rita Crews and my sister, Erin Crews for always standing by me and for their constant support throughout my life. I would also like to thank my extended family including my grandmother, aunts, uncles, in-laws, and cousins as well as friends who have always been tremendously supportive of me. I couldn’t have made it through this process without the support of all of these people. I would also like to thank my advisor, Dr. William Millard, for his guidance and understanding in helping me reach my goal. I truly value the independence I was allowed while working in his lab, and I appreciate the fact that he always knew when I needed help getting through the rough spots. I would also like to thank the other members of my supervisory committee: Dr. Joanna Peris, Dr. Maureen Keller-Wood, Dr. Michael Katovich, Dr. Steve Borst, and Dr. Ed Meyer for their valuable advice and for allowing me to use their laboratories and equipment as needed.
    [Show full text]
  • The Melanocortin-4 Receptor As Target for Obesity Treatment: a Systematic Review of Emerging Pharmacological Therapeutic Options
    International Journal of Obesity (2014) 38, 163–169 & 2014 Macmillan Publishers Limited All rights reserved 0307-0565/14 www.nature.com/ijo REVIEW The melanocortin-4 receptor as target for obesity treatment: a systematic review of emerging pharmacological therapeutic options L Fani1,3, S Bak1,3, P Delhanty2, EFC van Rossum2 and ELT van den Akker1 Obesity is one of the greatest public health challenges of the 21st century. Obesity is currently responsible for B0.7–2.8% of a country’s health costs worldwide. Treatment is often not effective because weight regulation is complex. Appetite and energy control are regulated in the brain. Melanocortin-4 receptor (MC4R) has a central role in this regulation. MC4R defects lead to a severe clinical phenotype with lack of satiety and early-onset severe obesity. Preclinical research has been carried out to understand the mechanism of MC4R regulation and possible effectors. The objective of this study is to systematically review the literature for emerging pharmacological obesity treatment options. A systematic literature search was performed in PubMed and Embase for articles published until June 2012. The search resulted in 664 papers matching the search terms, of which 15 papers remained after elimination, based on the specific inclusion and exclusion criteria. In these 15 papers, different MC4R agonists were studied in vivo in animal and human studies. Almost all studies are in the preclinical phase. There are currently no effective clinical treatments for MC4R-deficient obese patients, although MC4R agonists are being developed and are entering phase I and II trials. International Journal of Obesity (2014) 38, 163–169; doi:10.1038/ijo.2013.80; published online 18 June 2013 Keywords: MC4R; treatment; pharmacological; drug INTRODUCTION appetite by expressing anorexigenic polypeptides such as Controlling the global epidemic of obesity is one of today’s pro-opiomelanocortin and cocaine- and amphetamine-regulated most important public health challenges.
    [Show full text]
  • Brown Adipose Tissue Is Associated with Systemic Concentrations of Peptides Secreted from the Gastrointestinal System and Involv
    177:1 M Chondronikola and others BAT and GI-secreted peptides 177:1 33–40 Clinical Study Brown adipose tissue is associated with systemic concentrations of peptides secreted from the gastrointestinal system and involved in appetite regulation Maria Chondronikola1,2,3,4, Craig Porter1,5, Ioannis Malagaris1,2, Aikaterini A Nella1,6 and Labros S Sidossis1,2,4,5,7 1Metabolism Unit, Shriners Hospitals for Children-Galveston, Galveston, Texas, USA, 2Division of Rehabilitation Sciences, Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, Texas, USA, 3Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St Louis, Missouri, USA, 4Department of Nutrition and Dietetics, Harokopio University, Athens, Greece, Correspondence 5Department of Surgery, 6Division of Pediatric Endocrinology, Department of Pediatrics, University of Texas Medical should be addressed Branch, Galveston, Texas, USA, and 7Department of Kinesiology and Health, Rutgers University, New Brunswick, to L S Sidossis New Jersey, USA Email [email protected] Abstract Objective: Brown adipose tissue (BAT) has been proposed as a potential therapeutic target against obesity and its related metabolic conditions. Data from studies in rodents support a cross talk between BAT and other distal tissues. The relation between BAT and peptide hormones secreted from the gastrointestinal system (GI) and involved in appetite regulation is not known in humans. Design: We studied 18 men during thermoneutral conditions and mild non-shivering cold exposure (CE). Methods: 2-Deoxy-2-(18F)fluoro-D-glucose positron emission tomography-computed tomography scans were conducted after mild cold to measure BAT volume. Fasting serum concentration of GI-secreted peptides and peptides involved in European Journal European of Endocrinology appetite regulation were measured during thermoneutral conditions and mild CE.
    [Show full text]
  • The Role of Melanocortin-3 and -4 Receptor in Regulating Appetite, Energy Homeostasis and Neuroendocrine Function in the Pig
    39 The role of melanocortin-3 and -4 receptor in regulating appetite, energy homeostasis and neuroendocrine function in the pig C R Barb, A S Robertson1, J B Barrett, R R Kraeling and K L Houseknecht1 USDA-ARS, Russell Research Center, PO Box 5677, Athens, Georgia 30604, USA 1Pfizer Global Research and Development, Pfizer, Inc., Groton, Connecticut 06340, USA (Requests for offprints should be addressed to C R Barb; Email: [email protected]) Abstract A recently discovered class of receptors, melanocortin-3 of NDP-MSH, which exhibited both a stimulatory and an and -4 receptor (MC3/4-R), are located within the brain inhibitory effect on GH secretion in fasted animals. and modulate feed intake in rodents. Stimulation of the Treatment with agouti-related peptide, a natural brain receptor (agonist) inhibits feed intake whereas blockade hormone that blocks the MC3/4R, failed to stimulate (antagonist) of the receptor increases intake. Our knowl- feed intake. These results do not support the idea that edge of factors regulating voluntary feed intake in humans endogenous melanocortin pays a critical role in regulating and domestic animals is very limited. i.c.v. administration feed intake and pituitary hormone secretion in the pig. of an MC3/4-R agonist, NDP-MSH, suppressed SHU9119 blocked the NDP-MSH-induced increase in (P,0·05) feed intake compared with controls at 12, 24, 48 cAMP in HEK293 cells expressing the porcine MC4-R and 72 h after treatment in growing pigs. Fed pigs were sequence without the missense mutation. The EC50 and more responsive to the MC3/4-R agonist then fasted IC50 values were similar to the human MC4-R, confirm- animals.
    [Show full text]
  • Pathophysiology of Melanocortin Receptors and Their Accessory Proteins
    Pathophysiology of melanocortin receptors and their accessory proteins Novoselova TV, Chan LF & Clark AJL Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ United Kingdom Correspondence to: Tatiana Novoselova PhD [email protected] 4845 words 4 Figures Abstract The melanocortin receptors (MCRs) and their accessory proteins (MRAPs) are involved in regulation of a diverse range of endocrine pathways. Genetic variants of these components result in phenotypic variation and disease. The MC1R is expressed in skin and variants in the MC1R gene are associated with ginger hair colour. The MC2R mediates the action of ACTH in the adrenal gland to stimulate glucocorticoid production and MC2R mutations result in familial glucocorticoid deficiency (FGD). MC3R and MC4R are involved in metabolic regulation and their gene variants are associated with severe pediatric obesity, whereas the function of MC5R remains to be fully elucidated. MRAPs have been shown to modulate the function of MCRs and genetic variants in MRAPs are associated with diseases including FGD type 2 and potentially early onset obesity. This review provides an insight into recent advances in MCRs and MRAPs physiology, focusing on the disorders associated with their dysfunction. Key words melanocortin, melanocortin receptors, accessory proteins, MRAP, MRAP2, ACTH, G-protein coupled receptors, obesity, adrenal gland, glucocorticoids, familial glucocorticoid deficiency, metabolism, hypothalamus 2 The Melanocortin system Melanocortins are a diverse group of peptides that regulate distinct physiological functions. They are the products of the pro-opiomelanocortin precursor peptide (POMC), which is predominantly produced in humans by the corticotroph cells of the anterior pituitary[1].
    [Show full text]
  • Melanocortin-4 Receptor: a Novel Signalling Pathway Involved in Body Weight Regulation
    International Journal of Obesity (1999) 23, Suppl 1, 54±58 ß 1999 Stockton Press All rights reserved 0307±0565/99 $12.00 http://www.stockton-press.co.uk/ijo Melanocortin-4 receptor: A novel signalling pathway involved in body weight regulation SL Fisher1, KA Yagaloff1 and P Burn1* 1Department of Metabolic Diseases, Hoffmann LaRoche, Nutley, NJ 07110, USA For many years, genetically obese mouse strains have provided models for human obesity. The Avy=-agouti mouse, one of the oldest obese mouse models, is characterized by maturity-onset obesity and diabetes as a result of ectopic expression of the secreted protein hormone, agouti protein. Agouti protein is normally expressed in hair follicles to regulate pigmentation through antagonism of the melanocortin-1 receptor, but in-vitro studies have demonstrated that the hormone also has potent antagonist activity for the melanocortin-4 receptor (MC4-R). Subsequent develop- ment of the MC4-R knockout mouse model demonstrated that MC4-R plays a role in weight homeostasis as these mice recapitulated the metabolic defects of the agouti mouse. Further evidence for this hypothesis was obtained from pharmacological studies utilizing peptides with MC4-R agonist activity, that inhibitied food intake (when administered intracerebrally). Additional studies with peptide antagonists have now implicated the MC4-R in the leptin signalling pathway. Finally, evidence that the MC4-R may play a role in human obesity has been obtained from the identi®cation of a dis-functional variant of the receptor in genetically obese subjects. Keywords: obesity; diabetes; agouti; melanocortin; POMC; leptin; ob Introduction There has been an explosion in obesity research and with this has come an understanding of the molecular mechanisms that underly the disease.
    [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]
  • Ghrelin, the GO Hormone.Indd
    Ghrelin, the “Go” Hormone by Ted Kyle, RPh, MBA, and William Hignett What if we could, for one day, create our bodies and Interesting Fact change them as we please to improve our physical nature? How would we enhance our strengths and What exactly is meant by address what we see as problems? How would we change our bodies and minds to alleviate stress, anxiety saying ghrelin is the hunger and physical problems? Related to weight, we would probably make it easier and very straightforward to lose hormone? pounds and fat and to keep the weight off our bodies. Th e ghrelin hormone, discovered in 1999, is released If we had this power, we might consider simplifying primarily from cells in the stomach and travels to the hormonal actions that fuel and curb hunger so these brain. Th ere, it interacts with both the hypothalamus actions are clear-cut and we comprehend exactly how (the brain’s physiological eating center) and the to lose weight. In fact, in real life, two hormones do brain’s pleasure centers to arouse hunger. appear to be this direct in their actions on eating and weight. Ghrelin (grell-in) is the hunger hormone and Th roughout the course of a day, ghrelin levels leptin is the stop appetite hormone. Many believe that naturally change dramatically, rising steeply before the actions of these “go and stop” appetite hormones a meal and then plummeting after eating. Ghrelin are straightforward, and that one is bad and the other stimulates the brain, which leads to an increase in is good.
    [Show full text]
  • Hypothalamic Agouti‐Related Peptide
    Journal of Neuroendocrinology, 2015, 27, 681–691 © 2015 The Authors. Journal of Neuroendocrinology published by ORIGINAL ARTICLE John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology Hypothalamic Agouti-Related Peptide mRNA is Elevated During Natural and Stress-Induced Anorexia I. C. Dunn*, P. W. Wilson*, R. B. D’Eath† and T. Boswell‡ *The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK. †Animal Behaviour & Welfare, Veterinary Science Research Group, SRUC, West Mains Road, Edinburgh, EH9 3JG, UK. ‡School of Biology, Centre for Behaviour and Evolution, Newcastle University, Newcastle-Upon-Tyne, UK. Journal of As part of their natural lives, animals can undergo periods of voluntarily reduced food intake Neuroendocrinology and body weight (i.e. animal anorexias) that are beneficial for survival or breeding, such as dur- ing territorial behaviour, hibernation, migration and incubation of eggs. For incubation, a change in the defended level of body weight or ‘sliding set point’ appears to be involved, although the neural mechanisms reponsible for this are unknown. We investigated how neuropeptide gene expression in the arcuate nucleus of the domestic chicken responded to a 60–70% voluntary reduction in food intake measured both after incubation and after an environmental stressor involving transfer to unfamiliar housing. We hypothesised that gene expression would not change in these circumstances because the reduced food intake and body weight represented a defended level in birds with free access to food. Unexpectedly, we observed increased gene expression of the orexigenic peptide agouti-related peptide (AgRP) in both incubating and trans- Correspondence to: ferred animals compared to controls.
    [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]