DOCSLIB.ORG

Interaction Between Substance P and TRH in the Control of Prolactin Release

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Interaction Between Substance P and TRH in the Control of Prolactin Release 373 Interaction between substance P and TRH in the control of prolactin release B H Duvilanski, D Pisera, A Seilicovich, M del Carmen Díaz, M Lasaga, E Isovich and M O Velardez Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Argentina (Requests for offprints should be addressed to B H Duvilanski, Centro de Investigaciones en Reproducción, Facultad de Medicina, Piso 10, Universidad de Buenos Aires, Paraguay 2155 (1121) Buenos Aires, Argentina; Email: [email protected]) Abstract Substance P (SP) may participate as a paracrine and/or release. In order to study the interaction between TRH autocrine factor in the regulation of anterior pituitary and SP on prolactin release, anterior pituitaries were function. This project studied the effect of TRH on SP incubated with either TRH (107 M) or SP, or with both content and release from anterior pituitary and the role of peptides. SP (107 and 106 M) by itself stimulated SP in TRH-induced prolactin release. TRH (107 M), prolactin release. While 107 M SP did not modify the but not vasoactive intestinal polypeptide (VIP), increased TRH effect, 106 M SP reduced TRH-stimulated pro- immunoreactive-SP (ir-SP) content and release from male lactin release. SP (105 M) alone failed to stimulate rat anterior pituitary in vitro. An anti-prolactin serum also prolactin release and markedly decreased TRH-induced increased ir-SP release and content. In order to determine prolactin release. The present study shows that TRH whether intrapituitary SP participates in TRH-induced stimulates ir-SP release and increases ir-SP content in the prolactin release, anterior pituitaries were incubated with anterior pituitary. Our data also suggest that SP may act as TRH (107 M) and either WIN 62,577, a specific a modulator of TRH effect on prolactin secretion by a antagonist of the NK1 receptor, or a specific anti-SP paracrine mechanism. 8 7 serum. Both WIN 62,577 (10 and 10 M) and the Journal of Endocrinology (2000) 166, 373–380 anti-SP serum (1:250) blocked TRH-induced prolactin Introduction rats (Yoshikawa & Hong 1983, Jessop et al. 1992). SP content in the anterior pituitary is regulated by several Substance P (SP), a neuropeptide belonging to the tachy- circulating hormones (De Palatis et al. 1985, Jonnassen kinin family, is found in most tissues, and produces a broad et al. 1987, Aronin et al. 1988, O’Halloran et al. 1990, range of cellular responses. SP exerts its effects through Jones et al. 1994). a specific receptor in a G protein-linked family of SP modulates several anterior pituitary hormones (Jessop receptors. It enhances polyphosphoinositide breakdown et al. 1992). SP stimulates in vitro prolactin release from the and increases intracellular free calcium levels (Mau et al. anterior pituitary (Vijayan & McCann 1979, Seilicovich 1990, Mau & Saermark 1991). In the anterior pituitary, et al. 1993), while the blockade of intrapituitary SP with the preferred SP receptor, a neurokinin-1 (NK1) subtype specific SP antibodies decreases basal prolactin release of the tachykinin receptor family, is found exclusively in (Afione et al. 1990a). lactotrophs and gonadotrophs (Larsen et al. 1992). Thyrotropin-releasing hormone (TRH) is a hypo- SP is synthesized (Jessop et al. 1992) and released physiotropic neuropeptide that increases thyrotropin (Seilicovich et al. 1990, Arita et al. 1993) by the anterior (TSH) and prolactin secretion. TRH is synthesized not pituitary. SP was found to be localized only in only in the hypothalamus but also in a subpopulation of somatotrophs and thyrotrophs of male rats (Brown et al. somatotrophs in the anterior pituitary (Bruhn et al. 1994). 1991, Arita et al. 1994). Also SP-like immunoreactive Several studies have demonstrated the modulatory role innervation is present in the anterior pituitary, distributed of some pituitary peptides on hypothalamic neurotransmit- around secretory cells such as lactotrophs (Liu et al. 1996) ters and neuropeptides that regulate anterior pituitary and corticotrophs (Ju et al. 1991) and around blood vessels hormone secretion (Peillon et al. 1997). Interactions (Mikkelsen et al. 1989). between neurotransmitters and SP or vasoactive intestinal SP content and preprotachykinin mRNA vary with age polypeptide (VIP) at pituitary level (Afione et al. 1990a,b, and sex of the animals; it is higher in male than in female Duvilanski et al. 1990, Apfelbaum 1998), and also Journal of Endocrinology (2000) 166, 373–380 Online version via http://www.endocrinology.org 0022–0795/00/0166–373 2000 Society for Endocrinology Printed in Great Britain Downloaded from Bioscientifica.com at 09/24/2021 11:21:02AM via free access 374 B H DUVILANSKI and others · Interaction between SP and TRH between VIP and TRH (Balsa et al. 1996) have been dry ice and processed for SP determination. An aliquot of described. each medium was separated before acidification and stored Since SP has a paracrine effect on prolactin secretion, at 20 C until prolactin determination. the aim of this study was to ascertain whether anterior pituitary SP is involved in the effect of TRH on prolactin release. Therefore, we designed our experiments in order Static incubation of anterior pituitary glands to study: (1) the influence of SP blockade on the effect of Three pituitaries per tube were used to assay SP and TRH on prolactin release; (2) the effect of TRH on prolactin release in each incubation, and only one when anterior pituitary SP release and content; and (3) the prolactin release alone was studied. The pituitaries were interaction between TRH and SP in the control of pre-incubated for 60 min in 1 ml KRB buffer. Afterwards, prolactin release. the tissue was incubated for another 60 min, unless other- wise indicated, in 1 ml of fresh KRB buffer containing the different drugs studied. Controls were incubated with Materials and Methods medium alone or vehicle or normal rabbit serum (NRS). At the end of the incubation period, media were aspirated. Male Wistar rats (200–250 g) were kept in controlled Media and tissues were immediately acidified, frozen on conditions of light (12 h light : 12 h darkness) and tem- dry ice and processed for SP determination. An aliquot of perature (21–24 C). Lab chow and water were supplied medium was separated before acidification, and stored at and animals were allowed to feed ad libitum. The rats were 20 C until prolactin determination. WIN 62,577 is a kept according to the NIH Guide for the Care and Use of non-peptide NK1 receptor antagonist that binds to rat Laboratory Animals. Rats were killed by decapitation and brain homogenates with K values of 21 nM (Appel et al. the anterior pituitary lobes removed, then placed in i 1991). WIN 62,577 was dissolved in DMSO and diluted Krebs–Ringer bicarbonate buffer, pH 7·4, containing in KRB buffer. A final concentration of 0·02% DMSO 10 mM glucose, 25 mM Hepes, 0·1 mM bacitracin, 0·1% had no effect on basal prolactin release. ascorbic acid and 0·1% bovine serum albumin (KRB buffer). All drugs were purchased from Sigma (St Louis, MO, SP determination USA), except TRH, SP and VIP (Peninsula Lab. Inc., Belmont, CA, USA), and WIN 62,577 (Research Media and tissues were heated at 100 C for 5 min in 1 M Biochemical Int., Natick, MA, USA). Rat prolactin acetic acid. The tissues were then homogenized and both and NIDDK anti-prolactin serum (S-9) were kindly media and tissues centrifuged at 14 500 r.p.m. for 20 min. supplied by the National Hormone and Pituitary Program The supernatants were lyophilized and stored at 70 C (Torrance, CA, USA). until SP determination. SP was measured by double Rabbit anti-SP serum was prepared, characterized antibody radioimmunoassay with 125I-SP as tracer, as and tested as previously reported (Debeljuk et al. 1988). previously described (Seilicovich et al. 1990). The intra- This anti-serum showed no cross-reactivity with other and interassay coefficients of variation were under 10%. mammalian neuropeptides such as neurokinin A, neuro- Immunoreactive SP (ir-SP) was expressed as ng/mg pro- kinin B, VIP, neuromedin B and neurotensin when these tein. Protein concentration of tissue pellets was determined peptides were tested at doses 5000–10 000-fold higher by Lowry’s method. than those of SP. Prolactin determination Dynamic incubation of anterior pituitary glands. Pulse-chase experiments Prolactin was measured in the incubation medium by a double antibody radioimmunoassay, with kits provided by Five pituitaries were placed into a small perforated basket the National Hormone and Pituitary Program. Results and immersed in a tube containing 1 ml of KRB buffer were expressed in terms of rat prolactin RP-3 standard. and pre-incubated for 30 min at 37 C, in an atmosphere The intra- and interassay coefficients of variation were less of 95% O –5% CO , with constant shaking of 60 cycles 2 2 than 9%. per min. Basal release was then determined by incubating the baskets for two periods of 15 min in fresh KRB buffer. Afterwards, the baskets were transferred to a tube contain- ing TRH (107 M) and incubated for 5 min (TRH Statistical analysis pulse). Finally, post-stimulus release was assessed by incu- Results were expressed as means...s and evaluated bating the baskets for two periods of 15 min in KRB by the Student t-test or by one- or two-way analysis of buffer. Controls were run in parallel with KRB buffer variance (ANOVA) followed by Student–Newman–Keuls only. The media were immediately acidified, frozen on multiple comparison test for unequal replicates or Journal of Endocrinology (2000) 166, 373–380 www.endocrinology.org Downloaded from Bioscientifica.com at 09/24/2021 11:21:02AM via free access Interaction between SP and TRH · B H DUVILANSKI and others 375 Table 1 Effect of WIN 62,577 on basal and SP-induced prolactin release.
Load more

Recommended publications
  • Vasopressin Release from the Rat Hypothalamo-Neurohypophysial System: Effects of Tachykinin NK–1 and NK–2 Receptors Agonis
    Neuroendocrinology Letters No.4 August Vol.26, 2005 Copyright © 2005 Neuroendocrinology Letters ISSN 0172–780X www.nel.edu Vasopressin release from the rat hypothalamo-neurohy- pophysial system: Effects of tachykinin NK–1 and NK–2 receptors agonists and antagonists ARTICLE ORIGINAL Marlena Juszczak Department of Pathophysiology, Medical University of Lodz, Lodz, Poland. Correspondence to: Marlena Juszczak, Ph.D., D.Sc. Department of Pathophysiology Medical University of Lodz Narutowicza 60 90-136 Lodz, POLAND TEL/FAX: +48 42 6306187 [email protected] Submitted: July 7, 2004 Accepted: October 15, 2004 Key words: tachykinin receptors; substance P; neurokinin A; vasopressin Neuroendocrinol Lett 2005; 26(4):367–372 PMID: 16136007 NEL260405A13 © Neuroendocrinology Letters www.nel.edu Abstract OBJECTIVES: Present experiments were undertaken to study the influence of pep- tide NK–1 and NK–2 receptor agonists and antagonists as well as substance P and neurokinin A (the natural ligands for these tachykinin receptors) on vasopres- sin (AVP) secretion from the rat hypothalamo-neurohypophysial (HN) system in vitro. RESULTS: The results showed that both substance P and highly selective tachykinin 9 11 NK–1 receptor agonist, i.e., [Sar ,Met(O2) ]-Substance P, enhanced significantly AVP secretion, while the NK–1 receptor antagonist (Tyr6,D–Phe7,D–His9)-Sub- stance P (6–11) – sendide – was found to antagonize the substance P–induced hormone release from isolated rat HN system (all peptides at the concentration of 10–7 M/L). The NK–2 receptor selective agonist (β–Ala8)–Neurokinin A (4–10) was essentially inactive in modifying AVP release from the rat HN system in vitro, while neurokinin A (the natural ligand for this tachykinin receptor) was found to stimulate the AVP release; this effect of neurokinin A has been diminished by the 5 6,8,9 10 NK–2 receptor antagonist (Tyr ,D–Trp ,Lys–NH2 )–Neurokinin A (4–10).
    [Show full text]
  • Neuromedin B Receptor Stimulation of Cav3.2 T-Type Ca 2+ Channels In
    Neuromedin B receptor stimulation of Cav3.2 T-type Ca2+ channels in primary sensory neurons mediates peripheral pain hypersensitivity Yuan Zhang 1, 3, #, *, Zhiyuan Qian 1, #, Dongsheng Jiang 2, #, Yufang Sun 3, 5, Shangshang Gao 3, Xinghong Jiang 3, 5, Hua Wang 4, *, Jin Tao 3, 5, * 1 Department of Geriatrics & Institute of Neuroscience, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China; 2 Comprehensive Pneumology Center, Helmholtz Zentrum München, Munich 81377, Germany; 3 Department of Physiology and Neurobiology & Centre for Ion Channelopathy, Medical College of Soochow University, Suzhou 215123, China; 4 Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; 5 Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou 215123, China # These authors contribute to this work equally Running title: NmbR facilitates Cav3.2 channels Individual email addresses for all authors: Yuan Zhang ([email protected]), Zhiyuan Qian ([email protected]), Dongsheng Jiang ([email protected]), Yufang Sun ([email protected]), Shangshang Gao ([email protected]), Xinghong Jiang ([email protected]), Hua Wang ([email protected]), Jin Tao ([email protected]) *To whom correspondence should be addressed: Dr. Yuan Zhang, Department of Geriatrics & Institute of Neuroscience, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China. E-mail: [email protected] Dr. Hua Wang, Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. E-mail: [email protected] Dr. Jin Tao, Department of Physiology and Neurobiology & Centre for Ion Channelopathy, Medical College of Soochow University, Suzhou 215123, China. E-mail: [email protected] 1 Abstract Background: Neuromedin B (Nmb) is implicated in the regulation of nociception of sensory neurons.
    [Show full text]
  • Europium-Labeled Ligands for Receptor Binding Studies
    Europium-labeled Ligands for Receptor Binding Studies Katja Sippola, Maija-Liisa Mäkinen, Sanna Rönnmark, Joni Helenius, Riitta Heilimö, Anu Koivikko, Pertti Hurskainen and Christel Gripenberg-Lerche PerkinElmer Life and Analytical Sciences, Wallac Oy 1 Introduction 2 Methods Time-resolved fluorescence enhancement technique DELFIA® enables development of highly sensitive assays for screening. We have developed a family of Europium-labeled peptides and proteins designed for ligand receptor binding assays that can be easily automated The DELFIA® ligand receptor binding assay is based on dissociation-enhanced time-resolved fluorescence. DELFIA® Eu-labeled ligand and and optimized either for 96 or 384 well format. These Eu-labeled ligands provide an excellent non-radioactive alternative that is both receptor membrane preparate are incubated on an filter plate (PALL AcroWell or AcroPrep) after which unbound labeled ligand is removed by stabile and sensitive. filtration. Eu is dissociated from the bound ligand by using DELFIA® Enhancement Solution. Dissociated Eu creates highly fluorescent complexes, ® The new tachycinin members of the DELFIA ligand family are Substance P and Neurokinin A. These peptide ligands have many which are measured in a multilabel counter with TRF option, e.g. EnVision™. physiological roles, e.g. they stimulate smooth muscle contraction and glandular secretion and are involved in immune responses and neurotransmission. 3 DELFIA® Neurokinin A assays on 96 well filtration plates 4 DELFIA® Substance P assays on 96 well
    [Show full text]
  • Role of Tachykinin Receptors and Melatonin in Oxytocin
    JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2004, 55, 4, 739749 www.jpp.krakow.pl M. JUSZCZAK, K. FURYKIEWICZ-NYKI, B. STEMPNIAK ROLE OF TACHYKININ RECEPTORS AND MELATONIN IN OXYTOCIN SECRETION FROM ISOLATED RAT HYPOTHALMO- NEUROHYPOPHYSIAL SYSTEM Department of Pathophysiology, Medical University of £ód, £ód, Poland Present investigations were undertaken to study the influence of peptide NK-1 and NK-2 receptor agonists and antagonists as well as substance P and neurokinin A (the natural ligands for these tachykinin receptors) on oxytocin (OT) release from isolated rat hypothalamo-neurohypophysial (H-N) system as well as to determine whether the tachykinin NK-1 and/or NK-2 receptors contribute to the response of oxytocinergic neurons to melatonin. The results show, for the first time, that highly selective NK- 9 11 1 receptor agonist, i.e., [Sar ,Met(O2) ]-Substance P, enhances while the NK-1 6 7 9 receptor antagonist (Tyr ,D-Phe ,D-His )-Substance P (6-11) - sendide - diminishes significantly OT secretion; the latter peptide was also found to antagonize the substance P-induced hormone release from isolated rat H-N system, when used at the -7 concentration of 10 M/L. Melatonin significantly inhibited basal and substance P- stimulated OT secretion. Neurokinin A and the NK-2 receptor selective agonist (ß- 8 5 6,8,9 Ala )-Neurokinin A (4-10) as well as the NK-2 receptor antagonist (Tyr ,D-Trp , 10 Lys-NH2 )-Neurokinin A (4-10) were essentially inactive in modifying OT release from the rat H-N system in vitro. The present data indicate a distinct role for tachykinin NK-1 (rather than NK-2) receptor in tachykinin-mediated regulation of OT secretion from the rat H-N system.
    [Show full text]
  • Substance P and Antagonists of the Neurokinin-1 Receptor In
    Martinez AN and Philipp MT, J Neurol Neuromed (2016) 1(2): 29-36 Neuromedicine www.jneurology.com www.jneurology.com Journal of Neurology & Neuromedicine Mini Review Article Open Access Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System Alejandra N. Martinez1 and Mario T. Philipp1,2* 1Division of Bacteriology & Parasitology, Tulane National Primate Research Center, Covington, LA, USA 2Department of Microbiology and Immunology, Tulane University Medical School, New Orleans, LA, USA Article Info ABSTRACT Article Notes This review addresses the role that substance P (SP) and its preferred receptor Received: May 03, 2016 neurokinin-1 (NK1R) play in neuroinflammation associated with select bacterial, Accepted: May 18, 2016 viral, parasitic, and neurodegenerative diseases of the central nervous system. *Correspondence: The SP/NK1R complex is a key player in the interaction between the immune Division of Bacteriology and Parasitology and nervous systems. A common effect of this interaction is inflammation. For Tulane National Primate Research Center this reason and because of the predominance in the human brain of the NK1R, Covington, LA, USA its antagonists are attractive potential therapeutic agents. Preventing the Email: [email protected] deleterious effects of SP through the use of NK1R antagonists has been shown © 2016 Philipp MT. This article is distributed under the terms of to be a promising therapeutic strategy, as these antagonists are selective, the Creative Commons Attribution 4.0 International License potent, and safe. Here we evaluate their utility in the treatment of different neuroinfectious and neuroinflammatory diseases, as a novel approach to Keywords clinical management of CNS inflammation.
    [Show full text]
  • Bombesin Receptors in Distinct Tissue Compartments of Human Pancreatic Diseases Achim Fleischmann, Ursula Läderach, Helmut Friess, Markus W
    0023-6837/00/8012-1807$03.00/0 LABORATORY INVESTIGATION Vol. 80, No. 12, p. 1807, 2000 Copyright © 2000 by The United States and Canadian Academy of Pathology, Inc. Printed in U.S.A. Bombesin Receptors in Distinct Tissue Compartments of Human Pancreatic Diseases Achim Fleischmann, Ursula Läderach, Helmut Friess, Markus W. Buechler, and Jean Claude Reubi Division of Cell Biology and Experimental Cancer Research (AF, UL, JCR), Institute of Pathology, University of Berne, and Department of Visceral and Transplantation Surgery (HF, MWB), Inselspital, University of Berne, Berne, Switzerland SUMMARY: Overexpression of receptors for regulatory peptides in various human diseases is reportedly of clinical interest. Among these peptides, bombesin and gastrin-releasing peptide (GRP) have been shown to play a physiological and pathophysiological role in pancreatic tissues. Our aim has been to localize bombesin receptors in the human diseased pancreas to identify potential clinical applications of bombesin analogs in this tissue. The presence of bombesin receptor subtypes has been evaluated in specimens of human pancreatic tissues with chronic pancreatitis (n ϭ 23) and ductal pancreatic carcinoma (n ϭ 29) with in vitro receptor autoradiography on tissue sections incubated with 125I-[Tyr4]-bombesin or the universal ligand 125I-[D-Tyr6, ␤-Ala11, Phe13, Nle14]-bombesin(6–14) as radioligands and displaced by subtype-selective bombesin receptor agonists and antagonists. GRP receptors were identified in the pancreatic exocrine parenchyma in 17 of 20 cases with chronic pancreatitis. No measurable bombesin receptors were found in the tumor tissue of ductal pancreatic carcinomas, however, GRP receptors were detected in a subset of peritumoral small veins in 19 of 29 samples.
    [Show full text]
  • Distribution of Neurokinin 2 and 3 Receptor Mrna in the Normal
    Distribution of Neurokinin 2 and 3 Receptor mRNA in the Normal Equine Gastrointestinal Tract and Effect of Inflammation on Expression of Neurokinin 1, 2 and 3 Receptor mRNA in the Jejunum by Dr. Christina Martin A Thesis presented to The University of Guelph In partial fulfillment of requirements for the degree of Masters of Science in Clinical Studies Guelph, Ontario, Canada Dr. Christina Martin, April, 2014 ABSTRACT DISTRIBUTION OF NEUROKININ 2 AND 3 RECEPTOR mRNA IN THE NORMAL EQUINE GASTROINTESTINAL TRACT AND EFFECT OF INFLAMMATION ON EXPRESSION OF NEUROKININ 1, 2 AND 3 RECEPTOR mRNA IN THE JEJUNUM Dr. Christina E. W. Martin Advisor: University of Guelph, 2014 Dr. Judith B. Koenig This study is an investigation of the distribution of neurokinin receptors in the equine gastrointestinal tract. The objectives of this research were to determine the relative distribution of neurokinin 2 (NK2) and 3 (NK3) receptor mRNA in the normal equine gastrointestinal tract, and also to determine changes in neurokinin 1 (NK1), NK2 and NK3 receptor mRNA expression after ischemia/reperfusion injury or intraluminal distension in the jejunum. Samples from 9 regions in the gastrointestinal tract (duodenum, jejunum, ileum, caecum, right ventral colon, left ventral colon, pelvic flexure, right dorsal colon and left dorsal colon) were harvested from 5 mature healthy horses, euthanized for reasons unrelated to the gastrointestinal tract, for the study of NK2 and NK3 mRNA distribution in the normal intestinal tract. To evaluate the effect of inflammation on NK1, NK2 and NK3 receptor mRNA distribution, samples were taken from 6 horses whose jejunum underwent one of three treatments: control (sham-operated), intraluminal distension (ILD) or ischemic strangulation obstruction and subsequent reperfusion injury (ISO).
    [Show full text]
  • The Significance of NK1 Receptor Ligands and Their Application In
    pharmaceutics Review The Significance of NK1 Receptor Ligands and Their Application in Targeted Radionuclide Tumour Therapy Agnieszka Majkowska-Pilip * , Paweł Krzysztof Halik and Ewa Gniazdowska Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland * Correspondence: [email protected]; Tel.: +48-22-504-10-11 Received: 7 June 2019; Accepted: 16 August 2019; Published: 1 September 2019 Abstract: To date, our understanding of the Substance P (SP) and neurokinin 1 receptor (NK1R) system shows intricate relations between human physiology and disease occurrence or progression. Within the oncological field, overexpression of NK1R and this SP/NK1R system have been implicated in cancer cell progression and poor overall prognosis. This review focuses on providing an update on the current state of knowledge around the wide spectrum of NK1R ligands and applications of radioligands as radiopharmaceuticals. In this review, data concerning both the chemical and biological aspects of peptide and nonpeptide ligands as agonists or antagonists in classical and nuclear medicine, are presented and discussed. However, the research presented here is primarily focused on NK1R nonpeptide antagonistic ligands and the potential application of SP/NK1R system in targeted radionuclide tumour therapy. Keywords: neurokinin 1 receptor; Substance P; SP analogues; NK1R antagonists; targeted therapy; radioligands; tumour therapy; PET imaging 1. Introduction Neurokinin 1 receptor (NK1R), also known as tachykinin receptor 1 (TACR1), belongs to the tachykinin receptor subfamily of G protein-coupled receptors (GPCRs), also called seven-transmembrane domain receptors (Figure1)[ 1–3]. The human NK1 receptor structure [4] is available in Protein Data Bank (6E59).
    [Show full text]
  • Neuromedins U and S Involvement in the Regulation of the Hypothalamo–Pituitary–Adrenal Axis
    REVIEW ARTICLE published: 05 December 2012 doi: 10.3389/fendo.2012.00156 Neuromedins U and S involvement in the regulation of the hypothalamo–pituitary–adrenal axis Ludwik K. Malendowicz*, Agnieszka Ziolkowska and Marcin Rucinski Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland Edited by: We reviewed neuromedin U (NMU) and neuromedin S (NMS) involvement in the regulation Hubert Vaudry, University of Rouen, of the hypothalamo–pituitary–adrenal (HPA) axis function. NMU and NMS are structurally France related and highly conserved neuropeptides. They exert biological effects via two GPCR Reviewed by: receptors designated as NMUR1 and NMUR2 which show differential expression. NMUR1 James A. Carr, Texas Tech University, USA is expressed predominantly at the periphery, while NMUR2 in the central nervous system. Gábor B. Makara, Hungarian Elements of the NMU/NMS and their receptors network are also expressed in the HPA Academy of Sciences, Hungary axis and progress in molecular biology techniques provided new information on their *Correspondence: actions within this system. Several lines of evidence suggest that within the HPA axis Ludwik K. Malendowicz, NMU and NMS act at both hypothalamic and adrenal levels. Moreover, new data suggest Department of Histology and Embryology, Poznan University of that NMU and NMS are involved in central and peripheral control of the stress response. Medical Sciences, 6 Swie¸cickiSt., 60-781 Poznan, Poland. Keywords: neuromedin U, neuromedin S, hypothalamus, pituitary, adrenal e-mail: [email protected] INTRODUCTION Identification of specific NMU receptors (NMUR1 and In search for new biologically active peptides, the group of NMUR2) and its anorexigenic action have enhanced interest in Minamino, Kangawa, and Matsuo in the 1980s isolated numerous physiological role of NMU and NMS (Howard et al., 2000; Ida small neuropeptides from porcine spinal cord.
    [Show full text]
  • The Role of Neuromedin B in the Regulation of Rat Pituitary-Adrenocortical Function
    Histol Histopathol (1 996) 1 1 : 895-897 Histology and Histopathology The role of neuromedin B in the regulation of rat pituitary-adrenocortical function L.K. ~alendowicz~,C. Macchi2, G.G. Nussdorfer2and M. Nowakl 'Department of Histology and Embryology, School of Medicine, Poznan, Poland and 2Department of Anatomy, University of Padua, Padua, ltaly Summary. The effects of a 7-day administration of NMB-receptor antagonist (NMB-A) (Kroog et al., neuromedin B (NMB) andlor (~~r~,D-phe12)-bornbesin, 1995). an NMB-receptor antagonist (NMB-A) on the function of pituitary-adrenocortical axis were investigated in Materials and methods the rat. NMB raised the plasma concentration of aldosterone, without affecting that of ACTH or Experimental procedure corticosterone; the simultaneous administration of NMB-A prevented the effect of NMB. Neither NMB nor Adult female Wistar rats (200k20 g body weight) NMB-A treatments induced significant changes in were kept under a 12:12 h light-dark cycle (illumination adenohypophysis and adrenal weights, nor in the average onset at 8:00 a.m.) at 23 T,and maintained on a volume of zona glomerulosa and zona reticularis cells. standard diet and tap water ad libitum. The rats were NMB-A administration lowered the volume of zona divided into equal groups (n=8), which were fasciculata cells, an effect annulled by the concomitant subcutaneously injected daily with NMB, NMB-A or NMB administration. Our results suggest that NMB NMB plus NMB-A (Bachem, Bubendorf, Switzerland) specifically stimulates aldosterone secretion, and that dissolved in 0.2 m1 0.9% NaC1, for 7 consecutive days. endogenous NMB or NMB-like peptides exert a tonic The dose was 1 nmo1/100 g body weight.
    [Show full text]
  • Tachykinins in Endocrine Tumors and the Carcinoid Syndrome
    European Journal of Endocrinology (2008) 159 275–282 ISSN 0804-4643 CLINICAL STUDY Tachykinins in endocrine tumors and the carcinoid syndrome Janet L Cunningham1, Eva T Janson1, Smriti Agarwal1, Lars Grimelius2 and Mats Stridsberg1 Departments of 1Medical Sciences and 2Genetics and Pathology, University Hospital, SE 751 85 Uppsala, Sweden (Correspondence should be addressed to J Cunningham who is now at Section of Endocrine Oncology, Department of Medical Sciences, Lab 14, Research Department 2, Uppsala University Hospital, Uppsala University, SE 751 85 Uppsala, Sweden; Email: [email protected]) Abstract Objective: A new antibody, active against the common tachykinin (TK) C-terminal, was used to study TK expression in patients with endocrine tumors and a possible association between plasma-TK levels and symptoms of diarrhea and flush in patients with metastasizing ileocecal serotonin-producing carcinoid tumors (MSPCs). Method: TK, serotonin and chromogranin A (CgA) immunoreactivity (IR) was studied by immunohistochemistry in tissue samples from 33 midgut carcinoids and 72 other endocrine tumors. Circulating TK (P-TK) and urinary-5 hydroxyindoleacetic acid (U-5HIAA) concentrations were measured in 42 patients with MSPCs before treatment and related to symptoms in patients with the carcinoid syndrome. Circulating CgA concentrations were also measured in 39 out of the 42 patients. Results: All MSPCs displayed serotonin and strong TK expression. TK-IR was also seen in all serotonin- producing lung and appendix carcinoids. None of the other tumors examined contained TK-IR cells. Concentrations of P-TK, P-CgA, and U-5HIAA were elevated in patients experiencing daily episodes of either flush or diarrhea, when compared with patients experiencing occasional or none of these symptoms.
    [Show full text]
  • Calcitonin Gene-Related Peptide and Other Peptides
    P1: KWW/KKL P2: KWW/HCN QC: KWW/FLX T1: KWW GRBT050-16 Olesen- 2057G GRBT050-Olesen-v6.cls July 9, 2005 4:30 ••Chapter 16 ◗ Calcitonin Gene-Related Peptide and Other Peptides Susan Brain and Lars Edvinsson Vasoactive peptides can be either stored or synthesized de THE CGRP FAMILY OF PEPTIDES novo before release from a range of tissues in the brain or from the walls of intracranial vasculature. In this chapter, The expression of mRNA from the calcitonin gene is tissue we concentrate on neuropeptides that are released from specific in that CGRP mRNA is predominantly expressed perivascular nerves. These include calcitonin gene-related in nerves and calcitonin mRNA in the thyroid (5). The 37 peptide (CGRP), substance P, neurokinin A, nociceptin, amino acid peptide CGRP belongs to a family that include somatostatin, and opioids (Table 16-1). The endothelium the more recently discovered peptides adrenomedullin produces the potent vasoconstrictors endothelin and an- that is primarily produced by non-neuronal tissues, espe- giotensin, and dilators such as nitric oxide, prostacyclin, cially vascular tissues and amylin that is mainly produced and endothelium-derived hyperpolarizing factors. In ad- in the pancreas. They share some structural homology (ap- dition there are circulating agents; among these the most proximately 25–40%) and also some, but not total, similar- potent is 5-hydroxytryptamine. The neuronal messengers ities in biological activities (see Brain and Grant [11] for stored in the intracranial vessels have been reviewed recent review). CGRP is abundant in the body and has a (32) and it was revealed that sympathetic nerves store wide distribution throughout the central and peripheral noradrenaline, neuropeptide Y, and ATP, the parasympa- nervous systems.
    [Show full text]