Characterisation, localisation and expression of porcine TACR1, TACR2 and TACR3 genes A., Podlasz P., Chmielewska-Krzesinska M., Wasowicz K. (2017): Characterisation, localisation and expression of porcine TACR1, TACR2 and TACR3 genes. Veterinarni Medicina, 62: 443-455.
download PDF
Substance P is involved in many physiological and pathophysiological processes. This functional diversity is mediated by three neurokinin receptor subtypes (NK1R, NK2R and NK3R) encoded by the TACR1, TACR2 and TACR3 genes, respectively. Despite the increasing interest in using pigs (Sus scrofa) to study human disease mechanisms, the sequences of these receptors are still unconfirmed or in the case of the NK1 receptor, not yet even unpredicted. We employed in silico analysis to define the localisation of the porcine tachykinin receptor genes, and to predict the structures and amino acid sequences of the respective proteins. A reverse transcription polymerase chain reaction (RT-PCR) assay was performed to analyse the expression of tachykinin receptor genes in different porcine tissues. The data show that the TACR1 gene is located on chromosome 3, TACR2 on chromosome 14 and TACR3 on chromosome 8. All three genes encode proteins with structures that incorporate features of G-protein-coupled receptors with sizes of 407, 381 and 464 amino acids, respectively. The receptors display a high degree of similarity to other mammalian neurokinin receptors. The NK1R subtype is expressed in both the central nervous system and peripheral tissues, while NK2R expression seems to be localised mostly to peripheral tissues. The expression of NK3R is found mainly in the central nervous system. This report provides for the first time the results of a comprehensive analysis of the structure and distribution of porcine NK1R, as well as other porcine neurokinin receptors and their genes. We hope that our data may offer an invaluable foundation for the future studies on the function of diverse tachykinin peptides in the central nervous system and peripheral tissues.
Almeida T. A., Rojo J., Nieto P. M., Pinto F. M., Hernandez M., Martín J. D., Candenas M. L. (2004): Tachykinins and Tachykinin Receptors: Structure and Activity Relationships. Current Medicinal Chemistry, 11, 2045-2081
Fernández Alvarez C, Debeljuk L, Dı́az Rodrı́guez E, Dı́az López B (2002): Developmental pattern of tachykinins during aging in several organs: effect of exogenous melatonin. Peptides, 23, 1617-1623
Augood S.J., Faull R.L.M., Love D.R., Emson P.C. (1996): Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington's disease: A detailed cellularin situ hybridization study. Neuroscience, 72, 1023-1036
Bahadory Forough, Moore Kate H., Liu Lu, Burcher Elizabeth (2013): Gene expression of muscarinic, tachykinin, and purinergic receptors in porcine bladder: comparison with cultured cells. Frontiers in Pharmacology, 4, -
Bai TR, Zhou D, Weir T, Walker B, Hegele R, Hayashi S, McKay K, Bondy GP, Fong T (1995): Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in inflammatory airway diseases. American Journal of Physiology 269, L309–L317.
Barnes K., Turner A.J., Kenny A.J. (1993): An immunoelectron microscopic study of pig substantia nigra shows co-localization of endopeptidase-24.11 with substance P. Neuroscience, 53, 1073-1082
Brylla Elke, Aust Gabriela, Geyer Maren, Uckermann Ortrud, Löffler Sabine, Spanel-Borowski Katharina (2005): Coexpression of preprotachykinin A and B transcripts in the bovine corpus luteum and evidence for functional neurokinin receptor activity in luteal endothelial cells and ovarian macrophages. Regulatory Peptides, 125, 125-133
Bukowski R. (2014): Expression of NK1 receptor at the protein and mRNA level in the porcine female reproductive system. Polish Journal of Veterinary Sciences, 17, -
Candenas Luz, Lecci Alessandro, Pinto Francisco M., Patak Eva, Maggi Carlo Alberto, Pennefather Jocelyn N. (2005): Tachykinins and tachykinin receptors: effects in the genitourinary tract. Life Sciences, 76, 835-862
Chen Yuejin, Hoover Donald B. (1995): Autoradiographic localization of NK1 and NK3 tachykinin receptors in rat kidney. Peptides, 16, 673-681
Czaja K, Wasowicz K, Klimczuk M, Podlasz P, Lakomy M (2001): Distribution and immunohistochemical characterisation of paracervical neurons innervating the oviduct in the pig. Folia Morphologica 60, 205–211.
Diemunsch Pierre, Gr??lot Laurent (2000): Potential of Substance P Antagonists as Antiemetics. Drugs, 60, 533-546
Fong Tung Ming, Yu Hong, Huang Ruey Ruey C., Strader Catherine D. (1992): The extracellular domain of the neurokinin-1 receptor is required for high-affinity binding of peptides. Biochemistry, 31, 11806-11811
Czeh Boldizsár, Simon Mária, van der Hart Marieke GC, Schmelting Barthel, Hesselink Mayke B, Fuchs Eberhard (): Chronic Stress Decreases the Number of Parvalbumin-Immunoreactive Interneurons in the Hippocampus: Prevention by Treatment with a Substance P Receptor (NK1) Antagonist. Neuropsychopharmacology, 30, 67-79
Garcia-Ortega J., Pinto F. M., Fernandez-Sanchez M., Prados N., Cejudo-Roman A., Almeida T. A., Hernandez M., Romero M., Tena-Sempere M., Candenas L. (): Expression of neurokinin B/NK3 receptor and kisspeptin/KISS1 receptor in human granulosa cells. Human Reproduction, 29, 2736-2746
GERARD NORMA P., GERARD CRAIG (1991): Molecular Cloning of the Human Neurokinin-2 Receptor cDNA by Polymerase Chain Reaction and Isolation of the Gene. Annals of the New York Academy of Sciences, 632, 389-390
Gerard Norma P., Bao Lu, Xiao-Ping He, Gerard Craig (1993): Molecular aspects of the tachykinin receptors. Regulatory Peptides, 43, 21-35
Goode T (): Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation. Gut, 47, 387-396
Green Stuart A., Alon Achilles, Ianus Juliana, McNaughton Kristin S., Tozzi Carol A., Reiss Theodore F. (2006): Efficacy and Safety of a Neurokinin-1 Receptor Antagonist in Postmenopausal Women With Overactive Bladder With Urge Urinary Incontinence. The Journal of Urology, 176, 2535-2540
Halliday G.M., Blumbergs P.C., Cotton R.G.H., Blessing W.W., Geffen L.B. (1990): Loss of brainstem serotonin- and substance P-containing neurons in Parkinson's disease. Brain Research, 510, 104-107
H�pp�l� O., Lakom M., Majewski M., Wasowicz K., Yanaihara N. (1993): Distribution of neuropeptides in the porcine stellate ganglion. Cell & Tissue Research, 274, 181-187
Hasenöhrl R.U., Souza-Silva M.A.De, Nikolaus S., Tomaz C., Brandao M.L., Schwarting R.K.W., Huston J.P. (2000): Substance P and its role in neural mechanisms governing learning, anxiety and functional recovery. Neuropeptides, 34, 272-280
Holm Ida E., Geneser Finn A., Zimmer Jens (1993): Cholecystokinin-, enkephalin-, and substance P-like immunoreactivity in the dentate area, hippocampus, and subiculum of the domestic pig. The Journal of Comparative Neurology, 331, 310-325
Holzer P (): Tachykinin receptors in the gut: physiological and pathological implications. Current Opinion in Pharmacology, 1, 583-590
Hoover Donald B., Chang Yingzi, Hancock John C., Zhang Lili (): Actions of Tachykinins Within the Heart and Their Relevance to Cardiovascular Disease.. The Japanese Journal of Pharmacology, 84, 367-373
Improta Giovanna, Broccardo Maria (2006): Tachykinins: Role in Human Gastrointestinal Tract Physiology and Pathology. Current Drug Targets, 7, 1021-1029
Kaleczyc J., Podlasz P., Winnicka A., Wasowicz W., Sienkiewicz W., Zmudzki J., Lakomy M. (2010): Characterization of Autonomic Nerve Markers and Lymphocyte Subsets in the Ileal Peyer’s Patch of Pigs Infected Experimentally with Brachyspira hyodysenteriae. Journal of Comparative Pathology, 143, 248-257
Kobilka Brian K. (2007): G protein coupled receptor structure and activation. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1768, 794-807
Lamb Jasmine P., Sparrow Malcolm P. (2002): Three-Dimensional Mapping of Sensory Innervation with Substance P in Porcine Bronchial Mucosa. American Journal of Respiratory and Critical Care Medicine, 166, 1269-1281
LARSEN P. J., MIKKELSEN J. D., SAERMARK T. (1989): Binding of a Iodinated Substance P Analog to a NK-1 Receptor on Isolated Cell Membranes from Rat Anterior Pituitary*. Endocrinology, 124, 2548-2557
Maggi Carlo Alberto (1995): The mammalian tachykinin receptors. General Pharmacology: The Vascular System, 26, 911-944
Mann Patricia T., Southwell Bridget R., Ding Yu-Qiang, Shigemoto Ryuichi, Mizuno Noboru, Furness John B. (1997): Localisation of neurokinin 3 (NK3) receptor immunoreactivity in the rat gastrointestinal tract. Cell and Tissue Research, 289, 1-9
MAPP CRISTINA E., MIOTTO DEBORAH, BRACCIONI FAUSTO, SAETTA MARINA, TURATO GRAZIELLA, MAESTRELLI PIERO, KRAUSE JAMES E., KARPITSKIY VLADIMIR, BOYD NORMAN, GEPPETTI PIERO, FABBRI LEONARDO M. (2000): The Distribution of Neurokinin-1 and Neurokinin-2 Receptors in Human Central Airways. American Journal of Respiratory and Critical Care Medicine, 161, 207-215
Massi Maurizio, Panocka Izabela, de Caro Giuseppe (2000): The psychopharmacology of tachykinin NK-3 receptors in laboratory animals. Peptides, 21, 1597-1609
Masu Yasuo, Nakayama Kazuhisa, Tamaki Hiromi, Harada Yoshio, Kuno Motoy, Nakanishi Shigetada (1987): cDNA eloping of bovine substance-K receptor through oocyte expression system. Nature, 329, 836-838
Meini Stefania, Patacchini Riccardo, Maggi Carlo Alberto (1994): Tachykinin NK1 receptor subtypes in the rat urinary bladder. British Journal of Pharmacology, 111, 739-746
Myers A C, Undem B J (1993): Electrophysiological effects of tachykinins and capsaicin on guinea-pig bronchial parasympathetic ganglion neurones.. The Journal of Physiology, 470, 665-679
Myers Allen, Undem Bradley, Kummer Wolfgang (1996): Anatomical and electrophysiological comparison of the sensory innervation of bronchial and tracheal parasympathetic ganglion neurons. Journal of the Autonomic Nervous System, 61, 162-168
Nakanishi S (1991): Mammalian Tachykinin Receptors. Annual Review of Neuroscience, 14, 123-136
Nussdorfer Gastone G., Malendowicz Ludwik K. (1998): Role of Tachykinins in the Regulation of the Hypothalamo–Pituitary–Adrenal Axis. Peptides, 19, 949-968
Otsuka M, Yoshioka K (1993): Neurotransmitter functions of mammalian tachykinins. Physiological Review 73, 229–308.
Page Nigel M. (2005): New challenges in the study of the mammalian tachykinins. Peptides, 26, 1356-1368
Pidsudko Z., Kaleczyc J., Wąsowicz K., Sienkiewicz W., Majewski M., Zając W., Łakomy M. (2008): Distribution and Chemical Coding of Intramural Neurons in the Porcine Ileum During Proliferative Enteropathy. Journal of Comparative Pathology, 138, 23-31
Pidsudko Z., Wasowicz K., Kaleczyc J., Klimczuk M., Bossowska A., Majewski M., Adriaensen D., Timmermans J.-P. (2011): The influence of ileitis on the neurochemistry of the caudal mesenteric ganglion in the pig. Neurogastroenterology & Motility, 23, e213-e222
Bockaert J. (): Molecular tinkering of G protein-coupled receptors: an evolutionary success. The EMBO Journal, 18, 1723-1729
Pinto Francisco M, Almeida Teresa A, Hernandez Mariano, Devillier Philippe, Advenier Charles, Candenas M.Luz (2004): mRNA expression of tachykinins and tachykinin receptors in different human tissues. European Journal of Pharmacology, 494, 233-239
PITZEL LUTZ, JARRY HUBERTUS, WUTTKE WOLFGANG (1991): Effects of Substance-P and Neuropeptide-Y on in Vitro Steroid Release by Porcine Granulosa and Luteal Cells*. Endocrinology, 129, 1059-1065
Podlasz P, Wasowicz K (2008): Neurochemical characteristics of paracervical ganglion in the pig. Veterinarni Medicina 53, 135–146.
Podlasz P, Wasowicz K, Kaleczyc J, Lakomy M, Bukowski R (2003): Localization of immunoreactivities for neuropeptides and neurotransmitter-synthesizing enzymes in the pterygopalatine ganglion of the pig. Veterinarni Medicina 48, 99–107.
Portbury Andrea L., Furness John B., Southwell Bridget R., Wong Helen, Walsh John H., Bunnett Nigel W. (1996): Distribution of neurokinin-2 receptors in the guinea-pig gastrointestinal tract. Cell and Tissue Research, 286, 281-292
Rameshwar P, Ganea D, Gascon P (1993): In vitro stimulatory effect of substance P on hematopoiesis. Blood 81, 391–398.
Renzi Daniela, Pellegrini Beatrice, Tonelli Francesco, Surrenti Calogero, Calabrò Antonio (2000): Substance P (Neurokinin-1) and Neurokinin A (Neurokinin-2) Receptor Gene and Protein Expression in the Healthy and Inflamed Human Intestine. The American Journal of Pathology, 157, 1511-1522
Cejudo Roman Antonio, Pinto Francisco M., Dorta Idaira, Almeida Teresa A., Hernández Mariano, Illanes Matilde, Tena-Sempere Manuel, Candenas Luz (2012): Analysis of the expression of neurokinin B, kisspeptin, and their cognate receptors NK3R and KISS1R in the human female genital tract. Fertility and Sterility, 97, 1213-1219
Saffroy M, Torrens Y, Glowinski J, Beaujouan J.-C (2003): Autoradiographic distribution of tachykinin NK2 binding sites in the rat brain: comparison with NK1 and NK3 binding sites. Neuroscience, 116, 761-773
Sakurada Tsukasa, Alufuzoff Irina, Winblad Bengt, Nordberg Agneta (1990): Substance P-like immunoreactivity, choline acetyltransferase activity and cholinergic muscarinic receptors in Alzheimer's disease and multi-infarct dementia. Brain Research, 521, 329-332
Sarau Henry M, Feild John A, Ames Robert S, Foley James J, Nuthulaganti Parvathi, Schmidt Dulcie B, Buckley Peter T, Elshourbagy Nabil A, Brawner Mary E, Luttmann Mark A, Giardina Giuseppe A.M, Hay Douglas W.P (2001): Molecular and pharmacological characterization of the murine tachykinin NK3 receptor. European Journal of Pharmacology, 413, 143-150
Schmidt Peter, Poulsen Steen S., Rasmussen Torben N., Bersani Maurizio, Holst Jens J. (1991): Substance P and neurokinin A are codistributed and colocalized in the porcine gastrointestinal tract. Peptides, 12, 963-973
Schmidt Peter Thelin, Torn??e Karen, Poulsen Steen Seier, Rasmussen Torben Norre, Holst Jens Juul (2000): Tachykinins in the Porcine Pancreas: Potent Exocrine and Endocrine Effects Via NK-1 Receptors. Pancreas, 20, 241-247
Severini C. (): The Tachykinin Peptide Family. Pharmacological Reviews, 54, 285-322
Spooren W, Riemer C, Meltzer H (2005): Opinion: NK3 receptor antagonists: the next generation of antipsychotics? Nature Reviews Drug Discovery 4, 967–975.
Spurlock ME, Gabler NK (2008): The development of porcine models of obesity and the metabolic syndrome. Journal of Nutrition 138, 397–402.
Sternini Catia, Su Dennis, Gamp Patrick D., Bunnett Nigel W. (1995): Cellular sites of expression of the neurokinin-1 receptor in the rat gastrointestinal tract. The Journal of Comparative Neurology, 358, 531-540
SUNDELIN Johan B., PROVVEDINI Diego M., WAHLESTEDT Claes R., LAURELL Henrik, POHL Jens S., PETERSON Per A. (1992): Molecular cloning of the murine substance K and substance P receptor genes. European Journal of Biochemistry, 203, 625-631
TAKAHASHI Kenzo, TANAKA Atsuo, HARA Masumi, NAKANISHI Shigetada (1992): The primary structure and gene organization of human substance P and neuromedin K receptors. European Journal of Biochemistry, 204, 1025-1033
Takeda Y., Chou K.B., Takeda J., Sachais B.S., Krause J.E. (1991): Molecular cloning, structural characterization and functional expression of the human substance P receptor. Biochemical and Biophysical Research Communications, 179, 1232-1240
Trout L, Corboz MR, Ballard ST (2001): Mechanism of substance P-induced liquid secretion across bronchial epithelium. American Journal of Physiology – Lung Cellular and Molecular Physiology 281, 639–645.
TSUCHIDA Kunihiro, SHIGEMOTO Ryuichi, YOKOTA Yoshifumi, NAKANISHI Shigetada (1990): Tissue distribution and quantitation of the mRNAs for three rat tachykinin receptors. European Journal of Biochemistry, 193, 751-757
Valero Marta Sofía, Fagundes Diego Santos, Grasa Laura, Arruebo María Pilar, Plaza Miguel Ángel, Murillo María Divina (): Contractile effect of tachykinins on rabbit small intestine. Acta Pharmacologica Sinica, 32, 487-494
Vigna SR, Bowden JJ, McDonald DM, Fisher J, Okamoto A, McVey DC, Payan DG, Bunnett NW (1994): Characterization of antibodies to the rat substance P (NK-1) receptor and to a chimeric substance P receptor expressed in mammalian cells. Journal of Neuroscience 14, 834–845.
Wang Hong (2002): Localization of neurokinin B receptor in mouse gastrointestinal tract. World Journal of Gastroenterology, 8, 172-
Zhang Quanshun, Widmer Giovanni, Tzipori Saul (2013): A pig model of the human gastrointestinal tract. Gut Microbes, 4, 193-200
Zubrzycka M, Janecka A (2000): Substance P: transmitter of nociception (Minireview). Endocrine Regulations 34, 195–201.
download PDF

© 2020 Czech Academy of Agricultural Sciences