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Gene Review

TAC3  -  tachykinin 3

Homo sapiens

Synonyms: HH10, NKB, NKNB, PRO1155, Tachykinin-3, ...
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Disease relevance of TAC3


Psychiatry related information on TAC3


High impact information on TAC3

  • Here we have cloned a complementary DNA from human placental messenger RNA encoding a precursor protein of 121 amino acids which gives rise to a mature peptide identical to the neuropeptide neurokinin B (NKB) of other mammalian species [3].
  • Individuals homozygous for the NKB complementation groups have fewer circulating NK cells than individuals heterozygous for these alleles and alleles of other complementation groups, possibly explaining the low activity of cells in these subjects [6].
  • RESULTS: Tachykinins produced concentration-dependent increases in tension in circular and longitudinal muscle strips, with the following order of potency: beta-Ala(8)-neurokinin (NK) A (4-10) > NKB > substance P, suggesting NK(2) receptor involvement [7].
  • In contrast, specific NK binding sites were not observed in any area of the human colon [1].
  • A methylation interference assay revealed the critical G residues (from -167 to -151) for the DNA-protein complex formation specific to the cytokine response, and within this region the novel kappaB sequence, the promoter distal kappaB (pdkappaB) element (5'-GGGGAAG TAC-3'), was identified [8].

Chemical compound and disease context of TAC3


Biological context of TAC3


Anatomical context of TAC3

  • 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 [15].
  • There is recent evidence that NKB is expressed by the syncytiotrophoblast of the human placenta, an organ that is not innervated [11].
  • The mammalian tachykinins [substance P and neurokinin (NK) A and NKB] elicited concentration-dependent contractions of human esophageal smooth muscle [16].
  • Binding sites for NK were not detected in any part of the human GI tract [17].
  • METHODS: Comparison of the time-activity curve (TAC) of the left hemiscrotum with those of the femoral artery and femoral muscle identified three types of scrotal TAC:TAC-1 peaked as rapidly as in the femoral artery; TAC-3, as slowly as in femoral muscle, and TAC-2, intermediate between these [18].

Associations of TAC3 with chemical compounds

  • A reverse transcription-polymerase chain reaction (RT-PCR) assay was used to analyse the expression of TAC1 and TAC3, the genes that encode substance P/neurokinin A and neurokinin B, respectively, and the genes encoding the tachykinin NK(1), NK(2) and NK(3) receptors in different human tissues [15].
  • We have also identified a residue (Leu292) which appears to play a minor role in the binding of substance P (SP) and neurokinin B (NKB) to the NK2 receptor [19].
  • NKB and [Lys5,methyl-Leu9,Nle10]NKA(4-10) displaced [3H]ALIE-124 binding but with lower potency, whereas senktide had no affinity [20].
  • Our data show that NKB is a dilator of the fetal vasculature, causing a maximal 25.1 +/- 4.5% (mean +/- SEM; n = 5) decrease in fetal-side arterial hydrostatic pressure (5- microM NKB bolus; effective concentration in the circulation, 1.89 nM) after preconstriction with U-46619 [11].
  • When experiments were repeated in the presence of SR140333 (0.1 microM), the curve for SP became monophasic and showed a significant shift to the right, whereas curves to NKA and NKB were unaffected [21].

Physical interactions of TAC3


Regulatory relationships of TAC3

  • All three spantides failed to antagonize NKB-induced calcium responses at the NK3 receptor [23].

Other interactions of TAC3

  • The mutant receptor Leu292-->Ser binds NKB and SP with approximately a 5-fold greater affinity in comparison with the wild type receptor while the affinity of NKA remains unaffected [19].
  • SP, NKA, NKB and FK888 exhibited similar affinities for [125I]-BH-SP binding sites in both guinea pig arteries and bronchi.(ABSTRACT TRUNCATED AT 250 WORDS)[24]
  • The potent and selective NK1 and NK3-receptor antagonists, SR 140333 and SR 142801 (both 0.1 microM), failed to inhibit contractions induced by SP or NKB [25].
  • Tachykinin receptor subtypes were initially defined using agonist potency rations for the endogenous ligands substance P (SP), neurokinin (NK) A, and NKB [26].
  • We propose that neurons containing estrogen receptor, SP, and NKB mRNAs participate in the hypothalamic circuitry regulating estrogen negative feedback in the human [13].

Analytical, diagnostic and therapeutic context of TAC3


  1. Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease. Mantyh, C.R., Gates, T.S., Zimmerman, R.P., Welton, M.L., Passaro, E.P., Vigna, S.R., Maggio, J.E., Kruger, L., Mantyh, P.W. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  2. Neurokinin A and neurokinin B in the human retina. Schmid, E., Leierer, J., Kieselbach, G., Teuchner, B., Kralinger, M., Fischer-Colbrie, R., Krause, J.E., Nguyen, Q.A., Haas, G., Stemberger, K., Troger, J. Peptides (2006) [Pubmed]
  3. Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia. Page, N.M., Woods, R.J., Gardiner, S.M., Lomthaisong, K., Gladwell, R.T., Butlin, D.J., Manyonda, I.T., Lowry, P.J. Nature (2000) [Pubmed]
  4. Establishment of a novel human ovarian cancer cell line with high anchorage-independent growth ability. Nishikawa, Y., Yoshida, Y., Kawahara, K., Kurokawa, T., Tajima, K., Kotsuji, F. Int. J. Oncol. (2003) [Pubmed]
  5. Three dimensional structure of mammalian tachykinin peptide neurokinin B bound to lipid micelles. Mantha, A.K., Chandrashekar, I.R., Baquer, N.Z., Cowsik, S.M. J. Biomol. Struct. Dyn. (2004) [Pubmed]
  6. Polymorphic Hh genes in the HLA-B(C) region control natural killer cell frequency and activity. Dubey, D.P., Alper, C.A., Mirza, N.M., Awdeh, Z., Yunis, E.J. J. Exp. Med. (1994) [Pubmed]
  7. Tachykinins contribute to nerve-mediated contractions in the human esophagus. Krysiak, P.S., Preiksaitis, H.G. Gastroenterology (2001) [Pubmed]
  8. Identification of a novel cytokine response element in the human IFN regulatory factor-1 gene promoter. Imanishi, D., Yamamoto, K., Tsushima, H., Miyazaki, Y., Kuriyama, K., Tomonaga, M., Matsuyama, T. J. Immunol. (2000) [Pubmed]
  9. Neurokinin B causes concentration-dependent relaxation of isolated human placental resistance vessels. Laliberte, C., DiMarzo, L., Morrish, D.W., Kaufman, S. Regul. Pept. (2004) [Pubmed]
  10. Response of isolated human neurogenic bladders to tachykinins. Ohmura, M., Kondo, A., Saito, M. Urologia internationalis. (1997) [Pubmed]
  11. Neurokinin B is a paracrine vasodilator in the human fetal placental circulation. Brownbill, P., Bell, N.J., Woods, R.J., Lowry, P.J., Page, N.M., Sibley, C.P. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  12. Tachykinins and tachykinin receptors in the gut, with special reference to NK2 receptors in human. Lecci, A., Capriati, A., Altamura, M., Maggi, C.A. Autonomic neuroscience : basic & clinical. (2006) [Pubmed]
  13. Hypertrophy and increased gene expression of neurons containing neurokinin-B and substance-P messenger ribonucleic acids in the hypothalami of postmenopausal women. Rance, N.E., Young, W.S. Endocrinology (1991) [Pubmed]
  14. A regulatory role for neurokinin B in placental physiology and pre-eclampsia. Page, N.M., Woods, R.J., Lowry, P.J. Regul. Pept. (2001) [Pubmed]
  15. mRNA expression of tachykinins and tachykinin receptors in different human tissues. Pinto, F.M., Almeida, T.A., Hernandez, M., Devillier, P., Advenier, C., Candenas, M.L. Eur. J. Pharmacol. (2004) [Pubmed]
  16. Tachykinin receptor expression and function in human esophageal smooth muscle. Kovac, J.R., Chrones, T., Preiksaitis, H.G., Sims, S.M. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  17. Substance P and substance K receptor binding sites in the human gastrointestinal tract: localization by autoradiography. Gates, T.S., Zimmerman, R.P., Mantyh, C.R., Vigna, S.R., Maggio, J.E., Welton, M.L., Passaro, E.P., Mantyh, P.W. Peptides (1988) [Pubmed]
  18. Hemodynamic evaluation of left testicular varicocele by scrotal scintigraphy. Minayoshi, K., Okada, H., Fujisawa, M., Yamasaki, K., Kamidono, S. Eur. Urol. (2001) [Pubmed]
  19. The ligand binding site of the neurokinin 2 receptor. Site-directed mutagenesis and identification of neurokinin A binding residues in the human neurokinin 2 receptor. Bhogal, N., Donnelly, D., Findlay, J.B. J. Biol. Chem. (1994) [Pubmed]
  20. High affinity binding of [3H]propionyl-[Met(O2)11]substance P(7-11), a tritiated septide-like peptide, in Chinese hamster ovary cells expressing human neurokinin-1 receptors and in rat submandibular glands. Sagan, S., Beaujouan, J.C., Torrens, Y., Saffroy, M., Chassaing, G., Glowinski, J., Lavielle, S. Mol. Pharmacol. (1997) [Pubmed]
  21. Characterization of the [125I]-neurokinin A binding site in the circular muscle of human colon. Warner, F.J., Comis, A., Miller, R.C., Burcher, E. Br. J. Pharmacol. (1999) [Pubmed]
  22. Establishment of a cellular assay system for G protein-linked receptors: coupling of human NK2 and 5-HT2 receptors to phospholipase C activates a luciferase reporter gene. Weyer, U., Schäfer, R., Himmler, A., Mayer, S.K., Bürger, E., Czernilofsky, A.P., Stratowa, C. Recept. Channels (1993) [Pubmed]
  23. Comparison of antagonist activity of spantide family at human neurokinin receptors measured by aequorin luminescence-based functional calcium assay. Janecka, A., Poels, J., Fichna, J., Studzian, K., Vanden Broeck, J. Regul. Pept. (2005) [Pubmed]
  24. Differences in the distribution and characteristics of tachykinin NK1 binding sites between human and guinea pig lung. Walsh, D.A., Salmon, M., Featherstone, R., Wharton, J., Church, M.K., Polak, J.M. Br. J. Pharmacol. (1994) [Pubmed]
  25. In vitro characterization of tachykinin NK2-receptors modulating motor responses of human colonic muscle strips. Croci, T., Aureggi, G., Manara, L., Emonds-Alt, X., Le Fur, G., Maffrand, J.P., Mukenge, S., Ferla, G. Br. J. Pharmacol. (1998) [Pubmed]
  26. Neurokinin receptors subserving bronchoconstriction. Ellis, J.L. Can. J. Physiol. Pharmacol. (1995) [Pubmed]
  27. Gene regulation of neurokinin B and its receptor NK3 in late pregnancy and pre-eclampsia. Page, N.M., Dakour, J., Morrish, D.W. Mol. Hum. Reprod. (2006) [Pubmed]
  28. Localization of neurons expressing substance P and neurokinin B gene transcripts in the human hypothalamus and basal forebrain. Chawla, M.K., Gutierrez, G.M., Young, W.S., McMullen, N.T., Rance, N.E. J. Comp. Neurol. (1997) [Pubmed]
  29. Contractile response of the human isolated urinary bladder to neurokinins: involvement of NK-2 receptors. Maggi, C.A., Santicioli, P., Patacchini, R., Cellerini, M., Turini, D., Barbanti, G., Beneforti, P., Rovero, P., Meli, A. Eur. J. Pharmacol. (1988) [Pubmed]
  30. Sexual dimorphism in the organization of the rat hypothalamic infundibular area. Ciofi, P., Leroy, D., Tramu, G. Neuroscience (2006) [Pubmed]
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