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TAC1  -  tachykinin, precursor 1

Homo sapiens

Synonyms: Hs.2563, NK2, NKA, NKNA, NPK, ...
 
 
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Disease relevance of TAC1

 

Psychiatry related information on TAC1

  • A synopsis of the available data indicates that endogenous substance P and NKA interact with other enteric transmitters in the physiological control of gastrointestinal motor activity [6].
  • In order to measure tenderness (pressure pain threshold, PPT) more objectively, the usefulness of an algometer was evaluated [7].
 

High impact information on TAC1

 

Chemical compound and disease context of TAC1

  • Although a decline in HIV RNA equivalents was seen in all collection devices after 30 h, a significantly greater decline in plasma HIV RNA equivalents occurred in acid citrate dextrose VACUTAINER tubes than in citrate CPT, PPT, and standard EDTA VACUTAINER tubes [12].
  • Therefore, the PPT sequence may, in a gene therapy setting, be beneficial to prostate cancer patients that have been treated with androgen withdrawal [13].
  • The influence of inhaled phosphoramidon (a potent NEP inhibitor) was examined against the NKA-induced bronchospasm in a double-blind, placebo-controlled randomized study [14].
  • Similarly, bromocriptine treatment which induced only mild dyskinesia attenuated the MPTP-induced elevation in PPE-A mRNA in the caudate nucleus and putamen with no effect on reduced striatal PPT or PPE-B mRNA [15].
  • Overall there was no significant difference in striatal PPT, PPE-A and A2a receptor mRNA levels between normal animals and all L-DOPA (plus carbidopa and/or entacapone)-treated animals irrespective of whether or not dyskinesia occurred [16].
 

Biological context of TAC1

  • Thirteen residues in the human neurokinin 2 (NK2) receptor were identified as potential ligand-binding residues by molecular modeling and amino acid sequence analysis [17].
  • 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)[18]
  • Altogether, these results indicate that, even when there is a significant redundance in the effects of TKs and in the role of their receptors, the selective blockade of tachykinin NK2 receptors can have functional consequences on human intestinal motility and perception, but this can occur without the disruption of the physiological functions [19].
  • Methylation was associated with messenger RNA down-regulation for both SST and TAC1 [3].
  • The delta-PPT transcript present in the immune cells lacks exons 4 and 6 [20].
 

Anatomical context of TAC1

  • Specific [125I]NKA binding was detected in brains from neonatal rat, and to a lesser level in adult rat, gerbil, and guinea pig; it was not detected in monkey or human brain, but was present in circular muscle of human duodenum, confirming that this ligand binds to human NK2 receptors under our experimental conditions [21].
  • Tachykinin NK1 and NK2 receptors mediate non-adrenergic non-cholinergic excitatory neuromuscular transmission in the human ileum [22].
  • These results indicate that NK2 and also some NK1 receptors are present in monocytes isolated from healthy donors [23].
  • GRP and tachykinins (SP and NKA) from sensory nerves, and VIP released during parasympathetic reflexes may significantly stimulate mucous and serous cell secretion from human nasal mucosa in vivo [24].
  • In isolated human small intestine and colon circular muscle strips, both NK1 and NK2 receptors mediate contractile effects [19].
 

Associations of TAC1 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 [25].
  • The rank order of potency for NK2 antagonists was SR48968 > or = MEN11420 > GR94800 > or = MEN10627 > MEN10376 > or = R396 [26].
  • SB 223412 was selective for hNK-3 receptors compared with hNK-1 (>10,000-fold selective) and hNK-2 receptors (>140-fold selective), and selectivity was further demonstrated by its lack of effect, in concentrations up to 1 or 10 microM, in >60 receptor, enzyme and ion channel assays [27].
  • OBJECTIVE: The role of tachykinins such as neurokinin A in regulating bladder function is unclear, but NK2 receptors seem to mediate contraction in the human bladder and it has been suggested that these peptides may have a role in the pathophysiology of bladder dysfunction [28].
  • The differential changes in contractility found in IBD and ICC are specific to NK2 receptors, and may reflect the altered levels of substance P or other tachykinins found in these intestinal disorders [2].
 

Physical interactions of TAC1

  • Lastly, TRPC6 coimmunoprecipitated with the NKA pump when the proteins were coexpressed in Spodoptera frugiperda insect cells using recombinant baculoviruses [29].
  • Analogues of [Leu10]NKA4-10 were synthesized in which each of the amide bonds was sequentially replaced with the reduced amide psi (CH2NH) bond to determine the effect of this structural modification on the antagonism of NKA binding to the HUB NK2 receptor [30].
  • The order of potency of the three neurokinins substance P, neurokinin A and neuromedin K was consistent with published data and results from ligand binding studies performed with the same NK2 test cell line [31].
 

Regulatory relationships of TAC1

  • A single mutation of the neurokinin-2 (NK2) receptor prevents agonist-induced desensitization. Divergent conformational requirements for NK2 receptor signaling and agonist-induced desensitization in Xenopus oocytes [32].
 

Other interactions of TAC1

  • In organ bath experiments on guinea-pig colon MEN 11420 produced a concentration-dependent rightward shift of the concentration-response curve to the NK2 receptor selective agonist, [beta Ala8]neurokinin A (NKA) (4-10) with a pKB value of 8 [33].
  • Neurokinin receptors (NK1, NK2, NK3) are G-protein-coupled receptors, which upon activation by a peptide agonist induce a transient increase in the concentration of intracellular calcium [34].
  • 3. The rank order of potency of tachykinin and selective receptor agonists in contracting circular muscle strips was NKA > or = [Lys5,MeLeu9,Nle10]NKA(4-10) > or = neuropeptide (NP)gamma > or = [betaAla8]NKA(4-10) >> NKB > substance P (SP) >> senktide approximate to [Pro9]SP [35].
  • RESULTS: Cyst fluid K+ was directly correlated with cyst volume, cyst NKA inhibitory activity (in ouabain equivalents), and cyst concentrations of calcitonin, GRP, and CGRP [36].
  • Cyst fluid Na+ was inversely correlated with cyst fluid K+, cyst NKA inhibitory activity, cyst volume, and cyst fluid concentrations of calcitonin, GRP, and CGRP [36].
 

Analytical, diagnostic and therapeutic context of TAC1

  • Northern blot analysis visualized a single band of approximately 1300 bases, confirming the postmortem stability of PPT mRNA [37].
  • Semen analysis showed improved total motile sperm counts in 58.8, 69.2 and 26.7% of TAC-1, TAC-2, and TAC-3 patients, respectively [38].
  • Purification and separation of the individual compounds were achieved by NK2 assay-guided fractionation using gel filtration, reverse phase chromatography and HPLC [39].
  • The NKA-like immunoreactivities were further characterized by reversed phase HPLC in the rat TG and the human iris-ciliary body complex [40].
  • METHODS: The presence and distribution of NKA was examined in human eyes by radioimmunoassay and immunofluorescence [40].

References

  1. 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]
  2. Differential alterations in tachykinin NK2 receptors in isolated colonic circular smooth muscle in inflammatory bowel disease and idiopathic chronic constipation. Menzies, J.R., McKee, R., Corbett, A.D. Regul. Pept. (2001) [Pubmed]
  3. A genome-wide search identifies epigenetic silencing of somatostatin, tachykinin-1, and 5 other genes in colon cancer. Mori, Y., Cai, K., Cheng, Y., Wang, S., Paun, B., Hamilton, J.P., Jin, Z., Sato, F., Berki, A.T., Kan, T., Ito, T., Mantzur, C., Abraham, J.M., Meltzer, S.J. Gastroenterology (2006) [Pubmed]
  4. Pharmacological characterization of cloned human NK-2 (neurokinin A) receptor expressed in a baculovirus/Sf-21 insect cell system. Aharony, D., Little, J., Powell, S., Hopkins, B., Bundell, K.R., McPheat, W.L., Gordon, R.D., Hassall, G., Hockney, R., Griffin, R. Mol. Pharmacol. (1993) [Pubmed]
  5. Tachykinin-induced increase in gastric mucosal resistance: role of primary afferent neurons, CGRP, and NO. Stroff, T., Plate, S., Ebrahim, J.S., Ehrlich, K.H., Respondek, M., Peskar, B.M. Am. J. Physiol. (1996) [Pubmed]
  6. Tachykinins in the gut. Part I. Expression, release and motor function. Holzer, P., Holzer-Petsche, U. Pharmacol. Ther. (1997) [Pubmed]
  7. Acupuncture in the treatment of patients with craniomandibular disorders. Comparative, longitudinal and methodological studies. List, T. Swedish dental journal. Supplement. (1992) [Pubmed]
  8. Tachykinins contract the circular muscle of the human esophageal body in vitro via NK2 receptors. Huber, O., Bertrand, C., Bunnett, N.W., Pellegrini, C.A., Nadel, J.A., Debas, H.T., Geppetti, P. Gastroenterology (1993) [Pubmed]
  9. CHIF, a member of the FXYD protein family, is a regulator of Na,K-ATPase distinct from the gamma-subunit. Béguin, P., Crambert, G., Guennoun, S., Garty, H., Horisberger, J.D., Geering, K. EMBO J. (2001) [Pubmed]
  10. Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis. Singh, D., Joshi, D.D., Hameed, M., Qian, J., Gascón, P., Maloof, P.B., Mosenthal, A., Rameshwar, P. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  11. Functional expression of a novel human neurokinin-3 receptor homolog that binds [3H]senktide and [125I-MePhe7]neurokinin B, and is responsive to tachykinin peptide agonists. Krause, J.E., Staveteig, P.T., Mentzer, J.N., Schmidt, S.K., Tucker, J.B., Brodbeck, R.M., Bu, J.Y., Karpitskiy, V.V. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  12. Comparative stabilities of quantitative human immunodeficiency virus RNA in plasma from samples collected in VACUTAINER CPT, VACUTAINER PPT, and standard VACUTAINER tubes. Holodniy, M., Mole, L., Yen-Lieberman, B., Margolis, D., Starkey, C., Carroll, R., Spahlinger, T., Todd, J., Jackson, J.B. J. Clin. Microbiol. (1995) [Pubmed]
  13. A novel TARP-promoter-based adenovirus against hormone-dependent and hormone-refractory prostate cancer. Cheng, W.S., Kraaij, R., Nilsson, B., van der Weel, L., de Ridder, C.M., Tötterman, T.H., Essand, M. Mol. Ther. (2004) [Pubmed]
  14. Inhibition of neutral endopeptidase potentiates bronchoconstriction induced by neurokinin A in asthmatic patients. Crimi, N., Palermo, F., Oliveri, R., Polosa, R., Magrì, S., Mistretta, A. Clin. Exp. Allergy (1994) [Pubmed]
  15. Alterations in striatal neuropeptide mRNA produced by repeated administration of L-DOPA, ropinirole or bromocriptine correlate with dyskinesia induction in MPTP-treated common marmosets. Tel, B.C., Zeng, B.Y., Cannizzaro, C., Pearce, R.K., Rose, S., Jenner, P. Neuroscience (2002) [Pubmed]
  16. Alterations in preproenkephalin and adenosine-2a receptor mRNA, but not preprotachykinin mRNA correlate with occurrence of dyskinesia in normal monkeys chronically treated with L-DOPA. Zeng, B.Y., Pearce, R.K., MacKenzie, G.M., Jenner, P. Eur. J. Neurosci. (2000) [Pubmed]
  17. 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]
  18. 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]
  19. 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]
  20. Identification of a delta isoform of preprotachykinin mRNA in human mononuclear phagocytes and lymphocytes. Lai, J.P., Douglas, S.D., Rappaport, E., Wu, J.M., Ho, W.Z. J. Neuroimmunol. (1998) [Pubmed]
  21. Species differences in tachykinin receptor distribution: further evidence that the substance P (NK1) receptor predominates in human brain. Rigby, M., O'Donnell, R., Rupniak, N.M. J. Comp. Neurol. (2005) [Pubmed]
  22. Tachykinin NK1 and NK2 receptors mediate non-adrenergic non-cholinergic excitatory neuromuscular transmission in the human ileum. Zagorodnyuk, V., Santicioli, P., Turini, D., Maggi, C.A. Neuropeptides (1997) [Pubmed]
  23. Tachykinin receptors on human monocytes: their involvement in rheumatoid arthritis. Brunelleschi, S., Bordin, G., Colangelo, D., Viano, I. Neuropeptides (1998) [Pubmed]
  24. The effects of neuropeptides on mucous glycoprotein secretion from human nasal mucosa in vitro. Mullol, J., Rieves, R.D., Baraniuk, J.N., Lundgren, J.D., Mérida, M., Hausfeld, J.H., Shelhamer, J.H., Kaliner, M.A. Neuropeptides (1992) [Pubmed]
  25. 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]
  26. 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]
  27. Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist. Sarau, H.M., Griswold, D.E., Potts, W., Foley, J.J., Schmidt, D.B., Webb, E.F., Martin, L.D., Brawner, M.E., Elshourbagy, N.A., Medhurst, A.D., Giardina, G.A., Hay, D.W. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  28. Depressed contractile responses to neurokinin A in idiopathic but not neurogenic overactive human detrusor muscle. Sellers, D.J., Chapple, C.R., W Hay, D.P., Chess-Williams, R. Eur. Urol. (2006) [Pubmed]
  29. Proteomic analysis of TRPC5- and TRPC6-binding partners reveals interaction with the plasmalemmal Na(+)/K(+)-ATPase. Goel, M., Sinkins, W., Keightley, A., Kinter, M., Schilling, W.P. Pflugers Arch. (2005) [Pubmed]
  30. A new class of high affinity ligands for the neurokinin A NK2 receptor: psi (CH2NR) reduced peptide bond analogues of neurokinin A4-10. Harbeson, S.L., Shatzer, S.A., Le, T.B., Buck, S.H. J. Med. Chem. (1992) [Pubmed]
  31. 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]
  32. A single mutation of the neurokinin-2 (NK2) receptor prevents agonist-induced desensitization. Divergent conformational requirements for NK2 receptor signaling and agonist-induced desensitization in Xenopus oocytes. Nemeth, K., Chollet, A. J. Biol. Chem. (1995) [Pubmed]
  33. MEN 11420, a potent and selective tachykinin NK2 receptor antagonist in the guinea-pig and human colon. Santicioli, P., Giuliani, S., Patacchini, R., Tramontana, M., Criscuoli, M., Maggi, C.A. Naunyn Schmiedebergs Arch. Pharmacol. (1997) [Pubmed]
  34. 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]
  35. Circular muscle contraction, messenger signalling and localization of binding sites for neurokinin A in human sigmoid colon. Warner, F.J., Liu, L., Lubowski, D.Z., Burcher, E. Clin. Exp. Pharmacol. Physiol. (2000) [Pubmed]
  36. Relationships of Na+ and K+ concentrations to GRP, CGRP, and calcitonin immunoreactivities and Na+,K(+)-ATPase (NKA) inhibitory activity in human breast cyst fluid. Weber, C.J., Kim, D., Costanzo, M., Morris, J., Howe, B., Ward, L., D'Agati, V., McDonald, T., O'Dorisio, T.M., Butler, V.P. Ann. Surg. Oncol. (1994) [Pubmed]
  37. Preprotachykinin gene expression in the human basal ganglia: characterization of mRNAs and pre-mRNAs produced by alternate RNA splicing. Bannon, M.J., Poosch, M.S., Haverstick, D.M., Mandal, A., Xue, I.C., Shibata, K., Dragovic, L.J. Brain Res. Mol. Brain Res. (1992) [Pubmed]
  38. Hemodynamic evaluation of left testicular varicocele by scrotal scintigraphy. Minayoshi, K., Okada, H., Fujisawa, M., Yamasaki, K., Kamidono, S. Eur. Urol. (2001) [Pubmed]
  39. A family of depsi-peptide fungal metabolites, as selective and competitive human tachykinin receptor (NK2) antagonists: fermentation, isolation, physico-chemical properties, and biological activity. Hedge, V.R., Puar, M.S., Dai, P., Pu, H., Patel, M., Anthes, J.C., Richard, C., Terracciano, J., Das, P.R., Gullo, V. J. Antibiot. (2001) [Pubmed]
  40. Neurokinin a is a main constituent of sensory neurons innervating the anterior segment of the eye. Schmid, E., Leierer, J., Doblinger, A., Laslop, A., Fischer-Colbrie, R., Humpel, C., Theodorsson, E., Teuchner, B., Lalehabbasi, D., Dragosits, E., Kunze, C., Philipp, W., Göttinger, W., Troger, J. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
 
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