Skip to main content
SpringerLink
Log in

Galanin-Like Peptide (GALP) Facilitates Thermogenesis via Synthesis of Prostaglandin E2 by Astrocytes in the Periventricular Zone of the Third Ventricle

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Administration of galanin-like peptide (GALP) leads to a decrease in both total food intake and body weight 24 h after injection, compared to controls. Moreover, GALP induces an increase in core body temperature. To elucidate the mechanism by which GALP exerts its effect on energy homeostasis, urethane-anesthetized rats were intracerebroventricularly injected with GALP or saline, after which oxygen consumption, heart rate, and body temperature were monitored for 4 h. In some cases, animals were also pretreated with the cyclooxygenase (COX) inhibitor, diclofenac, via intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. c-Fos expression in the brain was also examined after injection of GALP, and the levels of COX and prostaglandin E2 synthetase (PGES) mRNA in primary cultured astrocytes treated with GALP were analyzed by using qPCR. The i.c.v. injection of GALP caused biphasic thermogenesis, an effect which could be blocked by pretreatment with centrally (i.c.v.), but not peripherally (i.v.) administered diclofenac. c-Fos immunoreactivity was observed in astrocytes in the periventricular zone of the third ventricle. GALP treatment also increased COX-2 and cytosolic PGES, but not COX-1, microsomal PGES-1, or microsomal PGES-2 mRNA levels in cultured astrocytes. We, therefore, suggest that GALP elicits thermogenesis via a prostaglandin E2-mediated pathway in astrocytes of the central nervous system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Amaral ME, Barbuio R, Milanski M et al (2006) Tumor necrosis factor-alpha activates signal transduction in hypothalamus and modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic neurotransmitters. J Neurochem 98:203–212

    Article  PubMed  CAS  Google Scholar 

  • Cao C, Matsumura K, Ozaki M, Watanabe Y (1999) Lipopolysaccharide injected into the cerebral ventricle evokes fever through induction of cyclooxygenase-2 in brain endothelial cells. J Neurosci 19:716–725

    PubMed  CAS  Google Scholar 

  • Cao C, Matsumura K, Watanabe Y (1997) Induction of cyclooxygenase-2 in the brain by cytokines. Ann N Y Acad Sci 813:307–309

    Article  PubMed  CAS  Google Scholar 

  • Coleman RA, Smith WL, Narumiya S (1994) International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 46:205–229

    PubMed  CAS  Google Scholar 

  • Cryer B, Feldman M (1998) Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med 104:413–421

    Article  PubMed  CAS  Google Scholar 

  • Fraley GS, Shimada I, Baumgartner JW, Clifton DK, Steiner RA (2003) Differential patterns of Fos induction in the hypothalamus of the rat following central injections of galanin-like peptide and galanin. Endocrinology 144:1143–1146

    Article  PubMed  CAS  Google Scholar 

  • Fujiwara K, Adachi S, Usui K et al (2002) Immunocytochemical localization of a galanin-like peptide (GALP) in pituicytes of the rat posterior pituitary gland. Neurosci Lett 317:65–68

    Article  PubMed  CAS  Google Scholar 

  • Hosli E, Ledergerber M, Kofler A, Hosli L (1997) Evidence for the existence of galanin receptors on cultured astrocytes of rat CNS: colocalization with cholinergic receptors. J Chem Neuroanat 13:95–103

    Article  PubMed  CAS  Google Scholar 

  • Jakobsson PJ, Thoren S, Morgenstern R, Samuelsson B (1999) Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A 96:7220–7225

    Article  PubMed  CAS  Google Scholar 

  • Juréus A, Cunningham MJ, McClain ME, Clifton DK, Steiner RA (2000) Galanin-like peptide (GALP) is a target for regulation by leptin in the hypothalamus of the rat. Endocrinology 141:2703–2706

    Article  PubMed  Google Scholar 

  • Kageyama H, Kita T, Toshinai K et al (2006) Galanin-like peptide promotes feeding behaviour via activation of orexinergic neurones in the rat lateral hypothalamus. J Neuroendocrinol 18:33–41

    Article  PubMed  CAS  Google Scholar 

  • Kageyama H, Takenoya F, Kita T, Hori T, Guan JL, Shioda S (2005) Galanin-like peptide in the brain: effects on feeding, energy metabolism and reproduction. Regul Pept 126:21–26

    Article  PubMed  CAS  Google Scholar 

  • Kelly JF, Elias CF, Lee CE et al (2004) Ciliary neurotrophic factor and leptin induce distinct patterns of immediate early gene expression in the brain. Diabetes 53:911–920

    Article  PubMed  CAS  Google Scholar 

  • Kerr NC, Holmes FE, Wynick D (2000) Galanin-like peptide (GALP) is expressed in rat hypothalamus and pituitary, but not in DRG. Neuroreport 11:3909–3913

    Article  PubMed  CAS  Google Scholar 

  • Krasnow SM, Fraley GS, Schuh SM, Baumgartner JW, Clifton DK, Steiner RA (2003) A role for galanin-like peptide in the integration of feeding, body weight regulation, and reproduction in the mouse. Endocrinology 144:813–822

    Article  PubMed  CAS  Google Scholar 

  • Krasnow SM, Hohmann JG, Gragerov A, Clifton DK, Steiner RA (2004) Analysis of the contribution of galanin receptors 1 and 2 to the central actions of galanin-like peptide. Neuroendocrinology 79:268–277

    Article  PubMed  CAS  Google Scholar 

  • Kudo I, Murakami M (2005) Prostaglandin E synthase, a terminal enzyme for prostaglandin E2 biosynthesis. J Biochem Mol Biol 38:633–638

    Article  PubMed  CAS  Google Scholar 

  • Lang R, Berger A, Santic R et al (2005) Pharmacological and functional characterization of galanin-like peptide fragments as potent galanin receptor agonists. Neuropeptides 39:179–184, Epub 2005 Feb 2001

    Article  PubMed  CAS  Google Scholar 

  • Larm JA, Gundlach AL (2000) Galanin-like peptide (GALP) mRNA expression is restricted to arcuate nucleus of hypothalamus in adult male rat brain. Neuroendocrinology 72:67–71

    Article  PubMed  CAS  Google Scholar 

  • Lawrence CB, Baudoin FM, Luckman SM (2002) Centrally administered galanin-like peptide modifies food intake in the rat: a comparison with galanin. J Neuroendocrinol 14:853–860

    Article  PubMed  CAS  Google Scholar 

  • Lawrence CB, Williams T, Luckman SM (2003) Intracerebroventricular galanin-like peptide induces different brain activation compared with galanin. Endocrinology 144:3977–3984

    Article  PubMed  CAS  Google Scholar 

  • Man PS, Lawrence CB (2008) Interleukin-1 mediates the anorexic and febrile actions of galanin-like peptide. Endocrinology 149:5791–5802, Epub 2008 Jul 5710

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto H, Naraba H, Murakami M et al (1997) Concordant induction of prostaglandin E2 synthase with cyclooxygenase-2 leads to preferred production of prostaglandin E2 over thromboxane and prostaglandin D2 in lipopolysaccharide-stimulated rat peritoneal macrophages. Biochem Biophys Res Commun 230:110–114

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto H, Noguchi J, Takatsu Y et al (2001) Stimulation effect of galanin-like peptide (GALP) on luteinizing hormone-releasing hormone-mediated luteinizing hormone (LH) secretion in male rats. Endocrinology 142:3693–3696

    Article  PubMed  CAS  Google Scholar 

  • Matsumura K, Cao C, Ozaki M, Morii H, Nakadate K, Watanabe Y (1998) Brain endothelial cells express cyclooxygenase-2 during lipopolysaccharide-induced fever: light and electron microscopic immunocytochemical studies. J Neurosci 18:6279–6289

    PubMed  CAS  Google Scholar 

  • Mouihate A, Chen X, Pittman QJ (1998) Interleukin-1beta fever in rats: gender difference and estrous cycle influence. Am J Physiol 275:R1450–R1454

    PubMed  CAS  Google Scholar 

  • Murakami M, Naraba H, Tanioka T et al (2000) Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem 275:32783–32792

    Article  PubMed  CAS  Google Scholar 

  • Nakamura K, Kaneko T, Yamashita Y et al (1999) Immunocytochemical localization of prostaglandin EP3 receptor in the rat hypothalamus. Neurosci Lett 260:117–120

    Article  PubMed  CAS  Google Scholar 

  • Narumiya S, Sugimoto Y, Ushikubi F (1999) Prostanoid receptors: structures, properties, and functions. Physiol Rev 79:1193–1226

    PubMed  CAS  Google Scholar 

  • Ohtaki T, Kumano S, Ishibashi Y et al (1999) Isolation and cDNA cloning of a novel galanin-like peptide (GALP) from porcine hypothalamus. J Biol Chem 274:37041–37045

    Article  PubMed  CAS  Google Scholar 

  • Osaka T (2012) Thermoregulatory responses elicited by microinjection of l-glutamate and its interaction with thermogenic effects of GABA and prostaglandin E(2) in the preoptic area. Neuroscience 226:156–164

    Article  PubMed  CAS  Google Scholar 

  • Osborne PG, Onoe H, Watanabe Y (1994) GABAergic system inducing hyperthermia in the rat preoptic area: its independence of prostaglandin E2 system. Brain Res 661:237–242

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic, San Diego, CA

    Google Scholar 

  • Priller J, Haas CA, Reddington M, Kreutzberg GW (1998) Cultured astrocytes express functional receptors for galanin. Glia 24:323–328

    Article  PubMed  CAS  Google Scholar 

  • Rage F, Lee BJ, Ma YJ, Ojeda SR (1997) Estradiol enhances prostaglandin E2 receptor gene expression in luteinizing hormone-releasing hormone (LHRH) neurons and facilitates the LHRH response to PGE2 by activating a glia-to-neuron signaling pathway. J Neurosci 17:9145–9156

    PubMed  CAS  Google Scholar 

  • Seregi A, Doll S, Schobert A, Hertting G (1992) Functionally diverse purinergic P2Y-receptors mediate prostanoid synthesis in cultured rat astrocytes: the role of ATP-induced phosphatidyl-inositol breakdown. Eicosanoids 5(Suppl):S19–S22

    PubMed  Google Scholar 

  • Strokin M, Sergeeva M, Reiser G (2007) Prostaglandin synthesis in rat brain astrocytes is under the control of the n-3 docosahexaenoic acid, released by group VIB calcium-independent phospholipase A2. J Neurochem 102:1771–1782

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto Y, Shigemoto R, Namba T et al (1994) Distribution of the messenger RNA for the prostaglandin E receptor subtype EP3 in the mouse nervous system. Neuroscience 62:919–928

    Article  PubMed  CAS  Google Scholar 

  • Summy-Long JY, Hu S (2009) Peripheral osmotic stimulation inhibits the brain's innate immune response to microdialysis of acidic perfusion fluid adjacent to supraoptic nucleus. Am J Physiol Regul Integr Comp Physiol 297:R1532–R1545

    Article  PubMed  CAS  Google Scholar 

  • Takatsu Y, Matsumoto H, Ohtaki T et al (2001) Distribution of galanin-like peptide in the rat brain. Endocrinology 142:1626–1634

    Article  PubMed  CAS  Google Scholar 

  • Tanikawa N, Ohmiya Y, Ohkubo H et al (2002) Identification and characterization of a novel type of membrane-associated prostaglandin E synthase. Biochem Biophys Res Commun 291:884–889

    Article  PubMed  CAS  Google Scholar 

  • Tanioka T, Nakatani Y, Semmyo N, Murakami M, Kudo I (2000) Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. J Biol Chem 275:32775–32782

    Article  PubMed  CAS  Google Scholar 

  • Vazquez-Tello A, Fan L, Hou X et al (2004) Intracellular-specific colocalization of prostaglandin E2 synthases and cyclooxygenases in the brain. Am J Physiol Regul Integr Comp Physiol 287:R1155–R1163

    Article  PubMed  CAS  Google Scholar 

  • Watanabe K, Kurihara K, Suzuki T (1999) Purification and characterization of membrane-bound prostaglandin E synthase from bovine heart. Biochim Biophys Acta 1439:406–414

    Article  PubMed  CAS  Google Scholar 

  • Xu J, Chalimoniuk M, Shu Y et al (2003) Prostaglandin E2 production in astrocytes: regulation by cytokines, extracellular ATP, and oxidative agents. Prostaglandins Leukot Essent Fatty Acids 69:437–448

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Rivest S (1999) Distribution, regulation and colocalization of the genes encoding the EP2- and EP4-PGE2 receptors in the rat brain and neuronal responses to systemic inflammation. Eur J Neurosci 11:2651–2668

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research (C) (to HK nos. 21590222 and 24590241) and a Grant-in-Aid for Challenging Exploratory Research (to SS no. 21659059) from Japan Society for the Promotion of Science, and a Grant-in-Aid for Scientific Research on Innovative Areas (to SS no. 22126004) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Dr. Ohtaki of Takeda Pharmaceutical Co., Ltd., for providing us with GALP peptide. We thank Sachi Kato for her technical help.

Author information

Authors and Affiliations

  1. Faculty of Health Care, Kiryu University, Midori City, Gunma, 379-2392, Japan

    Haruaki Kageyama

  2. Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Haruaki Kageyama, Kei Endo, Li Hua Wang, Kazuo Ito, Mamiko Suzuki, Junichi Sakagami, Fumiko Takenoya & Seiji Shioda

  3. National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8636, Japan

    Toshimasa Osaka

  4. Institute for Regenerative Medicine, Texas A&M Health Science Center at Scott & White, Temple, TX, 76502-6954, USA

    Jun Watanabe

  5. Department of Exercise and Sports Physiology, Hoshi University School of Pharmacy and Pharmaceutical Science, Shinagawa-ku, Tokyo, 142-8501, Japan

    Fumiko Takenoya

Authors
  1. Haruaki Kageyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kei Endo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshimasa Osaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li Hua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kazuo Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mamiko Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Junichi Sakagami
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fumiko Takenoya
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Seiji Shioda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seiji Shioda.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kageyama, H., Endo, K., Osaka, T. et al. Galanin-Like Peptide (GALP) Facilitates Thermogenesis via Synthesis of Prostaglandin E2 by Astrocytes in the Periventricular Zone of the Third Ventricle. J Mol Neurosci 50, 443–452 (2013). https://doi.org/10.1007/s12031-013-9952-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-013-9952-4

Keywords

Search

Navigation