tachykinin receptors


Summary: Cell surface proteins that bind TACHYKININS with high affinity and trigger intracellular changes influencing the behavior of cells. Three classes of tachykinin receptors have been characterized, the NK-1; NK-2; and NK-3; which prefer, respectively, SUBSTANCE P; NEUROKININ A; and NEUROKININ B.

Top Publications

  1. Lecci A, Maggi C. Peripheral tachykinin receptors as potential therapeutic targets in visceral diseases. Expert Opin Ther Targets. 2003;7:343-62 pubmed
    ..Finally, there is preclinical evidence for hypothesising an effect of NK-3 receptor antagonists on the cardiovascular disturbance that characterises pre-eclampsia. Other more speculative applications are also mentioned. ..
  2. Patak E, Candenas M, Pennefather J, Ziccone S, Lilley A, Martin J, et al. Tachykinins and tachykinin receptors in human uterus. Br J Pharmacol. 2003;139:523-32 pubmed
    ..of tachykinins in the uteri of nonpregnant women, and to analyse the expression of preprotachykinins (PPT), tachykinin receptors and the cell-surface peptidase, neprilysin (NEP), in the myometrium from pregnant and nonpregnant women...
  3. Stacey A, Woodhall G, Jones R. Neurokinin-receptor-mediated depolarization of cortical neurons elicits an increase in glutamate release at excitatory synapses. Eur J Neurosci. 2002;16:1896-906 pubmed
    ..83, 2519-2525], whereas the terminals of neurons responsible for the NK1-receptor induced glutamate release may not bear these receptors. These results have implications for control of activity and epileptogenesis in cortical networks. ..
  4. Yoshimura M, Yonehara N. Alteration in sensitivity of ionotropic glutamate receptors and tachykinin receptors in spinal cord contribute to development and maintenance of nerve injury-evoked neuropathic pain. Neurosci Res. 2006;56:21-8 pubmed
    ..rat model) and estimated the effects of the intrathecal injection of drugs known to affect glutamate and tachykinin receptors. In sham-operated rats, the NMDA receptor agonist NMDA and AMPA-kinate receptor agonist RS-(5)-..
  5. Pintado C, Pinto F, Pennefather J, Hidalgo A, Baamonde A, Sanchez T, et al. A role for tachykinins in female mouse and rat reproductive function. Biol Reprod. 2003;69:940-6 pubmed
    ..reverse transcription-polymerase chain reaction assay was used to analyze the expression of tachykinins and tachykinin receptors in different types of reproductive cells from mice...
  6. Frieling T, Dobreva G, Weber E, Becker K, Rupprecht C, Neunlist M, et al. Different tachykinin receptors mediate chloride secretion in the distal colon through activation of submucosal neurones. Naunyn Schmiedebergs Arch Pharmacol. 1999;359:71-9 pubmed
    ..The results suggest the importance of NK-1- and NK-3-receptors on cholinergic and non-cholinergic submucosal neurones for secretory processes in the guinea-pig distal colon. ..
  7. Harris J, Joules C, Stanley C, Thomas P, Clarke R. Glutamate and tachykinin receptors in central sensitization of withdrawal reflexes in the decerebrated rabbit. Exp Physiol. 2004;89:187-98 pubmed
    ..NMDA glutamate receptors, as well as NK1, and NK3 receptors, and a non-selective blocker of all tachykinin receptors, were assessed for their effects on the magnitude and duration of the increase in reflexes induced by ..
  8. Ingi T, Kitajima Y, Minamitake Y, Nakanishi S. Characterization of ligand-binding properties and selectivities of three rat tachykinin receptors by transfection and functional expression of their cloned cDNAs in mammalian cells. J Pharmacol Exp Ther. 1991;259:968-75 pubmed
    ..sequence, and this comprehensive analysis indicated that a high and selective affinity of each of the tachykinin receptors is governed by interaction with several key amino acids under recognition of the fundamental core sequence ..
  9. de Man J, Boeckx S, Anguille S, de Winter B, De Schepper H, Herman A, et al. Functional study on TRPV1-mediated signalling in the mouse small intestine: involvement of tachykinin receptors. Neurogastroenterol Motil. 2008;20:546-56 pubmed publisher
    ..The TRPV1-mediated contraction does not involve activation of intrinsic enteric motor nerves. Of the TRPV1 antagonists tested, BCTC combined strong TRPV1 antagonism with TRPV1 selectivity. ..

More Information


  1. Holzer P, Holzer Petsche U. Tachykinin receptors in the gut: physiological and pathological implications. Curr Opin Pharmacol. 2001;1:583-90 pubmed
    ..It would therefore appear that tachykinin receptors, which in the digestive system are expressed in a cell-specific manner, represent attractive targets for ..
  2. Nagahama M, Morimitsu S, Kihara A, Akita M, Setsu K, Sakurai J. Involvement of tachykinin receptors in Clostridium perfringens beta-toxin-induced plasma extravasation. Br J Pharmacol. 2003;138:23-30 pubmed
    ..7 These results suggest that plasma extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK(1) receptors. ..
  3. Brylla E, Aust G, Geyer M, Uckermann O, Löffler S, Spanel Borowski K. 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. Regul Pept. 2005;125:125-33 pubmed
    ..This is the first evidence for functional tachykinin receptor activity in luteal ECs and ovarian macrophages from bovine CL...
  4. Almeida T, Rojo J, Nieto P, Pinto F, Hernandez M, Martin J, et al. Tachykinins and tachykinin receptors: structure and activity relationships. Curr Med Chem. 2004;11:2045-81 pubmed
    ..Until now, three tachykinin receptors termed NK1 (NK1R), NK2 (NK2R) and NK3 (NK3R) have been cloned in different species...
  5. Page N. Hemokinins and endokinins. Cell Mol Life Sci. 2004;61:1652-63 pubmed publisher
    ..Additionally, three orphan tachykinin gene-related peptides are identified on TAC4, in rabbit, EK-2 and in humans, EKC and EKD...
  6. Candenas M, Magraner J, Armesto C, Anselmi E, Nieto P, Martin J, et al. Changes in the expression of tachykinin receptors in the rat uterus during the course of pregnancy. Biol Reprod. 2001;65:538-43 pubmed
    ..The aim of the present study was to characterize the population of tachykinin receptors in the pregnant rat uterus and to assess their regulation during the course of pregnancy and after delivery...
  7. Ghosh P, Saha S, Bhattacharya S, Bhattacharya S, Mukherjee S, Roy S. Tachykinin family genes and their receptors are differentially expressed in the hypothyroid ovary and pituitary. Cell Physiol Biochem. 2007;20:357-68 pubmed
    ..Further investigation in this area could elucidate the possible mechanism of tachykinins' involvement in loss of sexual cyclicity and other reproductive disorders associated with hypothyroidism. ..
  8. Pennefather J, Lecci A, Candenas M, Patak E, Pinto F, Maggi C. Tachykinins and tachykinin receptors: a growing family. Life Sci. 2004;74:1445-63 pubmed
    ..The identification of additional tachykinins has reopened the debate of whether more tachykinin receptors exist. In this review, we summarize the current knowledge of tachykinins and their receptors.
  9. Belvisi M, Patacchini R, Barnes P, Maggi C. Facilitatory effects of selective agonists for tachykinin receptors on cholinergic neurotransmission: evidence for species differences. Br J Pharmacol. 1994;111:103-10 pubmed
    ..results suggest that tachykinins may play an important role in modulating cholinergic neurotransmission in rabbit (via NK1 and NK2 receptors) and guinea-pig airways (via NK1 receptor) but have no demonstrable effect on human airways ..
  10. Quartara L, Altamura M. Tachykinin receptors antagonists: from research to clinic. Curr Drug Targets. 2006;7:975-92 pubmed
    ..The clinical studies reported in the literature and the destiny of the clinical candidates, where available, will be reviewed. ..
  11. Tremblay L, Kemel M, Desban M, Gauchy C, Glowinski J. Distinct presynaptic control of dopamine release in striosomal- and matrix-enriched areas of the rat striatum by selective agonists of NK1, NK2, and NK3 tachykinin receptors. Proc Natl Acad Sci U S A. 1992;89:11214-8 pubmed
    ..sensitive in vitro microperfusion method, the effects of selective and potent agonists of NK1, NK2, and NK3 tachykinin receptors ([Pro9]SP, ([Lys5,MeLeu9,Nle10]NKA-(4-10), and [Pro7]NKB, respectively) on the presynaptic control of ..
  12. Rigby M, O Donnell R, Rupniak N. Species differences in tachykinin receptor distribution: further evidence that the substance P (NK1) receptor predominates in human brain. J Comp Neurol. 2005;490:335-53 pubmed
    Marked species differences in the distribution of central tachykinin receptors are reported but uncertainty remains about the ability of available ligands to detect NK2 and NK3 receptors in human brain...
  13. Zhang Y, Berger A, Milne C, Paige C. Tachykinins in the immune system. Curr Drug Targets. 2006;7:1011-20 pubmed
    ..A more detailed understanding of the interactions between tachykinins and immune cells may provide the basis for the development of new therapies for inflammatory and immune-mediated diseases. ..
  14. Lecci A, Altamura M, Capriati A, Maggi C. Tachykinin receptors and gastrointestinal motility: focus on humans. Eur Rev Med Pharmacol Sci. 2008;12 Suppl 1:69-80 pubmed
  15. Ravina C, Seda M, Pinto F, Orea A, Fernandez Sanchez M, Pintado C, et al. A role for tachykinins in the regulation of human sperm motility. Hum Reprod. 2007;22:1617-25 pubmed
    Tachykinins and tachykinin receptors are widely distributed in the male reproductive tract and appear to be involved in reproduction...
  16. Rumsey W, Aharony D, Bialecki R, Abbott B, Barthlow H, Caccese R, et al. Pharmacological characterization of ZD6021: a novel, orally active antagonist of the tachykinin receptors. J Pharmacol Exp Ther. 2001;298:307-15 pubmed
    ..These data indicate that ZD6021 is a potent, orally active antagonist of all three tachykinin receptors. This compound may be useful for future studies of tachykinin-related pathology such as asthma.
  17. Page N, Dakour J, Morrish D. Gene regulation of neurokinin B and its receptor NK3 in late pregnancy and pre-eclampsia. Mol Hum Reprod. 2006;12:427-33 pubmed
    ..05). The present data suggest that the increased placental expression of TAC3 is part of the mechanism leading to the increased circulating levels of NKB in pre-eclampsia. ..
  18. Ebner K, Sartori S, Singewald N. Tachykinin receptors as therapeutic targets in stress-related disorders. Curr Pharm Des. 2009;15:1647-74 pubmed
    ..However, substantial work remains to be done to clarify the precise mechanism of action of these compounds, as well as the potential of combining them with established and experimental therapies in order to boost efficacy. ..
  19. Patak E, Pinto F, Story M, Pintado C, Fleming A, Page N, et al. Functional and molecular characterization of tachykinins and tachykinin receptors in the mouse uterus. Biol Reprod. 2005;72:1125-33 pubmed
    The aim of this study was to analyze the function and expression of tachykinins, tachykinin receptors, and neprilysin (NEP) in the mouse uterus...
  20. Candenas L, Lecci A, Pinto F, Patak E, Maggi C, Pennefather J. Tachykinins and tachykinin receptors: effects in the genitourinary tract. Life Sci. 2005;76:835-62 pubmed
    ..The current data suggest that the genitourinary tract is a primary site of action of the tachykininergic system. ..
  21. Patacchini R, Maggi C. Peripheral tachykinin receptors as targets for new drugs. Eur J Pharmacol. 2001;429:13-21 pubmed
    ..Tachykinin receptor antagonists are expected to afford therapeutically relevant effects. ..
  22. Pennefather J, Patak E, Pinto F, Candenas M. Mammalian tachykinins and uterine smooth muscle: the challenge escalates. Eur J Pharmacol. 2004;500:15-26 pubmed
    ..The possible physiological and pathological roles of tachykinins, including hemokinins and endokinins, in normal and premature labour, stress-induced abortion and menstrual disorders are briefly discussed. ..
  23. Pinto F, Almeida T, Hernandez M, Devillier P, Advenier C, Candenas M. mRNA expression of tachykinins and tachykinin receptors in different human tissues. Eur J Pharmacol. 2004;494:233-9 pubmed
    ..We found, for the first time, that TAC3 and TACR3 mRNAs are expressed in human airways and pulmonary arteries and veins, providing further evidence for the involvement of this system in lung physiopathology. ..
  24. Satake H, Kawada T. Overview of the primary structure, tissue-distribution, and functions of tachykinins and their receptors. Curr Drug Targets. 2006;7:963-74 pubmed
  25. Goto T, Tanaka T. Tachykinins and tachykinin receptors in bone. Microsc Res Tech. 2002;58:91-7 pubmed
    ..The distribution of tachykinin-immunoreactive axons and neurokinin receptors suggests that tachykinins may directly modulate bone metabolism through neurokinin receptors. ..
  26. Spitznagel H, Baulmann J, Blume A, Unger T, Culman J. C-FOS expression in the rat brain in response to substance P and neurokinin B. Brain Res. 2001;916:11-21 pubmed
    ..On the other side, brain areas activated by neurokinin B are known to be involved in the central regulation of blood pressure, water and salt homeostasis or control of behaviour. ..
  27. Minami M, Endo T, Kikuchi K, Ihira E, Hirafuji M, Hamaue N, et al. Antiemetic effects of sendide, a peptide tachykinin NK1 receptor antagonist, in the ferret. Eur J Pharmacol. 1998;363:49-55 pubmed
    ..3%, P < 0.05). Since sendide does not penetrate the central nervous system, these results suggest that the antiemetic effects of sendide are due to the inhibition of NK1 and 5-HT3 receptors on the emetic peripheral detector sites. ..
  28. Hayes J, Del Negro C. Neurokinin receptor-expressing pre-botzinger complex neurons in neonatal mice studied in vitro. J Neurophysiol. 2007;97:4215-24 pubmed
  29. Andersson K. Bladder activation: afferent mechanisms. Urology. 2002;59:43-50 pubmed
    ..However, it is most likely that a cascade of inhibitory and stimulatory transmitters/mediators, as well as ATP, are involved in the transduction mechanisms underlying the activation of afferent fibers during bladder filling. ..
  30. Nabe T, Tsuzuike N, Ohtani Y, Mizutani N, Watanabe S, Fujii M, et al. Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea-pigs. Clin Exp Allergy. 2009;39:138-46 pubmed publisher
    ..Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model...
  31. Gallicchio M, Benetti E, Rosa A, Fantozzi R. Tachykinin receptor modulation of cyclooxygenase-2 expression in human polymorphonuclear leucocytes. Br J Pharmacol. 2009;156:486-96 pubmed publisher
    ..Natural and synthetic ligands selective for the tachykinin receptors were used to modulate COX-2 protein (measured with Western blotting) and activity [as prostaglandin E(2) (..
  32. Peroutka S. Neurogenic inflammation and migraine: implications for the therapeutics. Mol Interv. 2005;5:304-11 pubmed
    ..e., PPE and NV) in migraine pathophysiology. The data indicate that the PPE component of NI plays no significant role in migraine but that NV is likely to be involved in migraine pathophysiology...
  33. Torfs H, Akerman K, Nachman R, Oonk H, Detheux M, Poels J, et al. Functional analysis of synthetic insectatachykinin analogs on recombinant neurokinin receptor expressing cell lines. Peptides. 2002;23:1999-2005 pubmed
    ..A single C-terminal amino acid change can turn an STKR-agonist into an NK-agonist and vice versa. ..
  34. Chung K. Cough: potential pharmacological developments. Expert Opin Investig Drugs. 2002;11:955-63 pubmed
    ..Large scale trials of these novel compounds have not been carried out in cough in man but there is a serious need for more effective antitussives devoid of side effects. ..
  35. Chowdhury J, Nahar N. Effects of substance P on spontaneous contraction in the flexure region of the guinea pig colon. Mymensingh Med J. 2007;16:17-9 pubmed
    ..These results suggest that Substance P produce contraction by Ca(2+) influx and the Ca(2+) influx occurs by activating verapamil sensitive Ca(2+) channel. ..
  36. Pitteloud N, Durrani S, Raivio T, Sykiotis G. Complex genetics in idiopathic hypogonadotropic hypogonadism. Front Horm Res. 2010;39:142-53 pubmed publisher
    ..Future investigations of IHH should characterize the extent of the involvement of multiple genes in disease pathogenesis, and elucidate the contributions of epigenetic factors. ..
  37. Blackshaw L, Dent J. Lower oesophageal sphincter responses to noxious oesophageal chemical stimuli in the ferret: involvement of tachykinin receptors. J Auton Nerv Syst. 1997;66:189-200 pubmed
    ..These data indicate that intra-oesophageal acid causes substance P release from extrinsic afferent nerve endings which activates local inhibitory pathways to the LOS via NK-1 receptors. ..
  38. Onori L, Aggio A, Taddei G. Regulatory role of tachykinins on intestinal propulsive activity. Ital J Gastroenterol Hepatol. 1999;31:346-51 pubmed
    The role of NK1, NK2, NK3 tachykinin receptors in subserving intestinal peristalsis has been reviewed referring mainly to the latest advances in this field...
  39. Evangelista S. Involvement of tachykinins in intestinal inflammation. Curr Pharm Des. 2001;7:19-30 pubmed
    ..The body of preclinical data so far available seems to indicate that tachykinin antagonists might be a new therapeutic tool in the treatment of gut disorders. ..
  40. Page N. Characterization of the gene structures, precursor processing and pharmacology of the endokinin peptides. Vascul Pharmacol. 2006;45:200-8 pubmed
    ..Particular consideration is also given to the potential interactions of the endokinins with the short NK(1) receptor isoform and to speculation of whether there could be an "endokinin-sensitive" NK(1) binding site. ..
  41. Maggi C, Patacchini R. Tachykinin NK1 receptor in the guinea-pig isolated proximal urethra: characterization by receptor selective agonists and antagonists. Br J Pharmacol. 1992;106:888-92 pubmed
    ..Endogenous tachykinins released from peripheral endings of capsaicin-sensitive primary afferents produce urethral contraction by activating NK, receptors. ..
  42. Faisy C, Planquette B, Naline E, Risse P, Frossard N, Fagon J, et al. Acid-induced modulation of airway basal tone and contractility: role of acid-sensing ion channels (ASICs) and TRPV1 receptor. Life Sci. 2007;81:1094-102 pubmed
    ..Conversely, the pH-induced hyperresponsiveness involves sensory nerves-dependent ASICs and TRPV1, and an unknown epithelial component in response to acidosis. ..
  43. Ogier R, Wrobel L, Raggenbass M. Action of tachykinins in the hippocampus: facilitation of inhibitory drive to GABAergic interneurons. Neuroscience. 2008;156:527-36 pubmed publisher
    ..Depending on the precise balance between these effects, tachykinins may either activate or depress hippocampal network activity. ..
  44. Kemel M, Perez S, Godeheu G, Soubrie P, Glowinski J. Facilitation by endogenous tachykinins of the NMDA-evoked release of acetylcholine after acute and chronic suppression of dopaminergic transmission in the matrix of the rat striatum. J Neurosci. 2002;22:1929-36 pubmed
  45. Wallace J, McCafferty D, Sharkey K. Lack of beneficial effect of a tachykinin receptor antagonist in experimental colitis. Regul Pept. 1998;73:95-101 pubmed
  46. Bueno L. [Therapeutic targets]. Gastroenterol Clin Biol. 2009;33 Suppl 1:S59-67 pubmed publisher
    ..These clinical data have opened the door to promising future drugs able to prevent or blunt such permeability alteration, which therefore may constitute a pathophysiological treatment for IBS. ..
  47. Corander M, Challis B, Thompson E, Jovanovic Z, Loraine Tung Y, Rimmington D, et al. The effects of neurokinin B upon gonadotrophin release in male rodents. J Neuroendocrinol. 2010;22:181-7 pubmed publisher
    ..In male rodent models, NKB and kisspeptin have different effects upon gonadotrophin release and appear to interact in a complex manner. ..
  48. Chetty N, Irving H, Coupar I. Activation of 5-HT3 receptors in the rat and mouse intestinal tract: a comparative study. Br J Pharmacol. 2006;148:1012-21 pubmed
    ..The rat jejunum shows evidence of 5-HT uptake and inactivation processes as well as inhibitory nitrergic and nontachykinin excitatory pathways associated with the 5-HT(3)-induced response. ..
  49. Lecci A, Maggi C. Tachykinins as modulators of the micturition reflex in the central and peripheral nervous system. Regul Pept. 2001;101:1-18 pubmed
    ..The overall available information suggests that TK receptor antagonists may affect bladder motility/reflexes which occur during different pathological states, while having little influence on the normal motor bladder function. ..
  50. Doi T, Kamo I, Imai S, Okanishi S, Ishimaru T, Ikeura Y, et al. Effects of TAK-637, a tachykinin receptor antagonist, on lower urinary tract function in the guinea pig. Eur J Pharmacol. 1999;383:297-303 pubmed
    ..01 mg/kg, p.o. in unanesthetized guinea pigs. These results indicate that TAK-637 may be useful as pharmacotherapy for detrusor overactivity without decreasing voiding pressure or causing voiding difficulties. ..
  51. de Man J, de Winter B, De Schepper H, Herman A, Pelckmans P. Differential role of tachykinin NK3 receptors on cholinergic excitatory neurotransmission in the mouse stomach and small intestine. Br J Pharmacol. 2008;155:1195-203 pubmed publisher
    ..This indicates a physiological role for NK(3) receptors in mouse stomach contractility and a pathophysiological role in mouse intestinal contractility. ..
  52. Torfs H, Poels J, Detheux M, Dupriez V, Van Loy T, Vercammen L, et al. Recombinant aequorin as a reporter for receptor-mediated changes of intracellular Ca2+ -levels in Drosophila S2 cells. Invert Neurosci. 2002;4:119-24 pubmed
    ..The rank order of inhibitory potencies was spantide III > spantide II > spantide I. ..
  53. Ramnarine S, Hirayama Y, Barnes P, Rogers D. 'Sensory-efferent' neural control of mucus secretion: characterization using tachykinin receptor antagonists in ferret trachea in vitro. Br J Pharmacol. 1994;113:1183-90 pubmed
    ..Potent and selective tachykinin antagonists may have therapeutic potential in bronchial diseases such as asthma and chronic bronchitis in which neurogenic mucus hypersecretion may be aetiologically important. ..