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Gene Review

Tac1  -  tachykinin, precursor 1

Rattus norvegicus

Synonyms: Nka, Nkna, PPT, PPTA3, Ppt5fl, ...
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Disease relevance of Tac1


Psychiatry related information on Tac1

  • Inhibition of the L-arginine/NO pathway sensitizes the gut to tachykinin-stimulated motor activity [6].
  • The intrathecal administration of SR-48,968, a tachykinin NK(2) receptor antagonist, did not affect the visceral pain threshold of hypersensitive animals [7].
  • Huntington's disease: changes in tachykinin content in postmortem brains [8].
  • Repeated electroconvulsive shock increases tachykinin and cholecystokinin mRNA expression in ventral periaqueductal gray [9].
  • Consequently, the present study was conducted to evaluate the hypothesis that the tachykinin neuropeptide K can inhibit maternal behavior after injection into the ventromedial hypothalamus [10].
  • Exposure to the forced swim test, an animal model of depression, elevated substance P (SP) release in the lateral septum (LS) of the rat. Acute administration of L-882429 (a neurokinin 1 receptor [ NK1] antagonist) systemically (i.p.) or locally into the LS increased swimming/struggling (active stress-coping strategy; 'antidepressant' effect). This effect was blocked by intraseptal 5-HT(1A) antagonism (WAY-100635). Further experimentation revealed that the effect was most likely mediated by GABAergic interneurons and not a direct heterosynpatic regulation of 5-HT release by NK1 [11].
  • Acute (45 minutes) and chronic (10 days;45 minutes each day) immobilization stress both down-regulate NK1 mRNA in the rat hippocampus [12].
  • Acute i.p. injections of CP-96,345, SR 48968, and SR 142801 (selective NK1, NK2, and NK3 antagonists, respectively) all decreased immobility in the forced swim test. The antidepressant effects of each antagonist were comparable to two traditional antidepressants, amitriptyline and desipramine. [13]
  • The Flinders Sensitive Line (FSL) is an animal model of depression created by selective breeding of Sprague-Dawley rats for increased sensitivity to diisopropylfluorophosphate (DFP; an anticholinesterase). NKA-LI and SP-LI were decreased in striatum but increased in the frontal cortex of FSL rats compared to controls (Flinders Resistant Line rats). In addition, NPY-LI was decreased in the hippocampus of FSL rats. Lithium treatment (admixed in rat chow for six weeks) abolished NKA-LI and SP-LI but not NPY-LI differences. [14]

High impact information on Tac1


Chemical compound and disease context of Tac1


Biological context of Tac1


Anatomical context of Tac1


Associations of Tac1 with chemical compounds

  • The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays [27].
  • 4. These findings suggest a role for capsaicin-sensitive primary afferents and the primary afferent neuropeptides encoded by PPT and CGRP mRNA in the maintenance and spread of arthritis [1].
  • 1. Following the recent proposal that the selective agonist septide, ([pGlu6,Pro9]SP(6-11)), acts on a novel tachykinin receptor distinct from the 'classical' NK1 receptor, the aim of the study was to investigate the possible heterogeneity of tachykinin NK1 receptors in the rat urinary bladder [31].
  • This concept is further supported by the inability of AVP to mimic tachykinin inhibition of the gastric vasodilator response to acid back-diffusion [24].
  • Similar interactions were observed between QUIN and tachykinin or metabotropic glutamate agonists [32].

Physical interactions of Tac1


Regulatory relationships of Tac1

  • Potentiation of tachykinin-induced plasma protein extravasation by calcitonin gene-related peptide [35].
  • This study demonstrates the stability of tachykinin receptors in these peripheral tissues and indicates the suitability of post-mortem tissue as a valid control in future tachykinin receptor studies [36].
  • We show that the functional antagonism of dynorphin at the NK4 receptor is reversed by the non-specific opioid antagonist naloxone and that tachykinin-evoked responses at the NK4 receptor are inhibited by the non-peptide NK3 receptor antagonist SR142801 in a concentration dependent manner [37].
  • However, the inhibition of Fos expression induced by exogenous substance P indicates that actions at sites postsynaptic to tachykinin- and/or non-tachykinin-containing primary afferent terminals must also contribute to the antinociceptive actions of GABA(B) receptor agonists [38].
  • This response remained unchanged after pretreatment with the tachykinin NK1 receptor antagonist SR 140,333 (300 nmol/kg) but tended to be enhanced by the NK2 receptor antagonist MEN 10,627 (200 nmol/kg) [39].

Other interactions of Tac1

  • We also studied the effect of a selective inhibitor (captopril, 2.5 mg/kg) of the tachykinin-degrading enzyme kininase II [or angiotensin-converting enzyme (ACE)] on substance P-induced airway vasodilation [40].
  • However, on the side ipsilateral to the lesion, NPY, Gal and preprotachykinin (PPT) mRNAs appeared in Mes5 cell bodies [41].
  • These results suggest that endothelin-1 selectively inhibits the capsaicin-induced release of neurotransmitters from rat vas deferens and these effects are mediated via endothelin ET(A) receptors but not by tachykinin release [42].
  • OBJECTIVES: Present experiments 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 vasopressin (AVP) secretion from the rat hypothalamo-neurohypophysial (HN) system in vitro [43].
  • To identify epitopes that determine their selectivity for natural and synthetic tachykinin peptides, we constructed a series of chimeric NK1/NK3 receptors in which carboxyl-terminal segments of increasing length in the NK1 receptor were exchanged with the corresponding segments from the NK3 receptor [44].
  • SP depressed evoked excitatory postsynaptic currents (EPSCs) in the rat nucleus accumbens (NAc) in vitro and involved PKC and cAMP but not PKA signaling [45]. Morever, the SP-mediated synpatic depression of EPSCs and excitatory evoked postsynaptic potentials in the NAc was blocked by SCH23390 (a D1-like receptor antagonist) and 8-cyclopentyltheophylline (8-CPT; an adenosine A1 receptor blocker) but neither by sulpiride (a selective D2/D3 antagonist) nor by D-APV (a NMDA antagonist) [46]. In addition, SP depressed evoked inhibitory postsynaptic potentials in the NAc, an action which was blocked by SCH23390 and by 8-CPT, suggesting that SP in the NAc modulates both excitatory and inhibitory inputs using similar mechanisms [47].
  • WIN51708 (a rat-specific selective NK1 antagonist) did not modulate 5-HT reuptake in rat cortical synaptosomes, indicating that 5-HT transporter inhibition is not likely a mechansm of the assumed antidepressant profile of NK1 antagonists [48].

Analytical, diagnostic and therapeutic context of Tac1


  1. Neuropeptide gene expression and capsaicin-sensitive primary afferents: maintenance and spread of adjuvant arthritis in the rat. Donaldson, L.F., McQueen, D.S., Seckl, J.R. J. Physiol. (Lond.) (1995) [Pubmed]
  2. Fourth isoform of preprotachykinin messenger RNA encoding for substance P in the rat intestine. Khan, I., Collins, S.M. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  3. Stress-induced visceral hypersensitivity in female rats is estrogen-dependent and involves tachykinin NK1 receptors. Bradesi, S., Eutamene, H., Garcia-Villar, R., Fioramonti, J., Bueno, L. Pain (2003) [Pubmed]
  4. Lipopolysaccharide induces preprotachykinin gene expression. Huang, H.Y., Lai, Y.L. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  5. The non-peptide tachykinin antagonist, CP-96,345, is a potent inhibitor of neurogenic inflammation. Lembeck, F., Donnerer, J., Tsuchiya, M., Nagahisa, A. Br. J. Pharmacol. (1992) [Pubmed]
  6. Tachykinin-stimulated small bowel myoelectric pattern: sensitization by NO inhibition, reversal by neurokinin receptor blockade. Schmidt, P.T., Bozkurt, A., Hellström, P.M. Regul. Pept. (2002) [Pubmed]
  7. Role of tachykinin NK1, NK2 and NK3 receptors in the modulation of visceral hypersensitivity in the rat. Gaudreau, G.A., Plourde, V. Neurosci. Lett. (2003) [Pubmed]
  8. Huntington's disease: changes in tachykinin content in postmortem brains. Arai, H., Emson, P.C., Carrasco, L.H. Ann. Neurol. (1987) [Pubmed]
  9. Repeated electroconvulsive shock increases tachykinin and cholecystokinin mRNA expression in ventral periaqueductal gray. Lindefors, N., Brodin, K., Stiller, C.O., Persson, H., Brodin, E. Neuroscience (1991) [Pubmed]
  10. Microinjection of the tachykinin neuropeptide K into the ventromedial hypothalamus disrupts the hormonal onset of maternal behavior in female rats. Sheehan, T.P., Numan, M. J. Neuroendocrinol. (1997) [Pubmed]
  11. Neurokinin 1 receptor antagonism promotes active stress coping via enhanced septal 5-HT transmission. Ebner, K., Singewald, G.M., Whittle, N., Ferraguti, F., Singewald, N. Neuropsychopharmacology. (2008) [Pubmed]
  12. Hippocampal neurokinin-1 receptor and brain-derived neurotrophic factor gene expression is decreased in rat models of pain and stress. Duric, V., McCarson, K.E. Neuroscience. (2005) [Pubmed]
  13. Antidepressant-like effects of neurokinin receptor antagonists in the forced swim test in the rat. Dableh, L.J., Yashpal, K., Rochford, J., Henry, J.L. Eur. J. Pharmacol. (2005) [Pubmed]
  14. Changed concentrations of tachykinins and neuropeptide Y in brain of a rat model of depression: lithium treatment normalizes tachykinins. Husum, H., Vasquez, P.A., Mathé, A.A. Neuropsychopharmacology. (2001) [Pubmed]
  15. Molecular characterization of a functional cDNA encoding the rat substance P receptor. Hershey, A.D., Krause, J.E. Science (1990) [Pubmed]
  16. Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Yankner, B.A., Duffy, L.K., Kirschner, D.A. Science (1990) [Pubmed]
  17. Hypertonicity, but not hypothermia, elicits substance P release from rat C-fiber neurons in primary culture. Garland, A., Jordan, J.E., Necheles, J., Alger, L.E., Scully, M.M., Miller, R.J., Ray, D.W., White, S.R., Solway, J. J. Clin. Invest. (1995) [Pubmed]
  18. Substance P and somatostatin inhibit calcium channels in rat sympathetic neurons via different G protein pathways. Shapiro, M.S., Hille, B. Neuron (1993) [Pubmed]
  19. SSR240600 [(R)-2-(1-[2-[4-[2-[3,5-bis(trifluoromethyl)phenyl]acetyl]-2-(3,4-dichlorophenyl)-2-morpholinyl]ethyl]- 4-piperidinyl)-2-methylpropanamide], a centrally active nonpeptide antagonist of the tachykinin neurokinin-1 receptor: I. biochemical and pharmacological characterization. Emonds-Alt, X., Proietto, V., Steinberg, R., Oury-Donat, F., Vigé, X., Vilain, P., Naline, E., Daoui, S., Advenier, C., Le Fur, G., Maffrand, J.P., Soubrié, P., Pascal, M. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  20. An isobolographic analysis of the effects of N-methyl-D-aspartate and NK1 tachykinin receptor antagonists on inflammatory hyperalgesia in the rat. Ren, K., Iadarola, M.J., Dubner, R. Br. J. Pharmacol. (1996) [Pubmed]
  21. The novel NK1 receptor antagonist MK-0869 (L-754,030) and its water soluble phosphoryl prodrug, L-758,298, inhibit acute and delayed cisplatin-induced emesis in ferrets. Tattersall, F.D., Rycroft, W., Cumberbatch, M., Mason, G., Tye, S., Williamson, D.J., Hale, J.J., Mills, S.G., Finke, P.E., MacCoss, M., Sadowski, S., Ber, E., Cascieri, M., Hill, R.G., MacIntyre, D.E., Hargreaves, R.J. Neuropharmacology (2000) [Pubmed]
  22. Different tachykinin receptor subtypes are coupled to the phosphoinositide or cyclic AMP signal transduction pathways in rat submandibular cells. Laniyonu, A., Sliwinski-Lis, E., Fleming, N. FEBS Lett. (1988) [Pubmed]
  23. Structure, expression, and some regulatory mechanisms of the rat preprotachykinin gene encoding substance P, neurokinin A, neuropeptide K, and neuropeptide gamma. Carter, M.S., Krause, J.E. J. Neurosci. (1990) [Pubmed]
  24. Tachykinin inhibition of acid-induced gastric hyperaemia in the rat. Heinemann, A., Jocic, M., Herzeg, G., Holzer, P. Br. J. Pharmacol. (1996) [Pubmed]
  25. Identification and cDNA sequence of delta-preprotachykinin, a fourth splicing variant of the rat substance P precursor. Harmar, A.J., Hyde, V., Chapman, K. FEBS Lett. (1990) [Pubmed]
  26. Age differences in neurokinin A and substance P from the hypothalamus, pituitary, pineal gland, and striatum of the rat. Effect of exogenous melatonin. Fernández, C., Debeljuk, L., Díaz, E., Díaz, B. Peptides (2002) [Pubmed]
  27. Tachykinin systems in the spinal cord and basal ganglia: influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA. Sivam, S.P., Krause, J.E. J. Neurochem. (1992) [Pubmed]
  28. Tachykinin receptor and neutral endopeptidase gene expression in the rat uterus: characterization and regulation in response to ovarian steroid treatment. Pinto, F.M., Armesto, C.P., Magraner, J., Trujillo, M., Martín, J.D., Candenas, M.L. Endocrinology (1999) [Pubmed]
  29. Tachykinin-, calcitonin gene-related peptide-, and protein gene product 9.5-immunoreactive nerve fibers in alveolar walls of mammals. Nohr, D., Weihe, E. Neurosci. Lett. (1991) [Pubmed]
  30. Simultaneous quantitation of substance P-encoding preprotachykinin alternatively spliced mRNAs and substance P receptor NK-1 mRNA by an RNase protection assay. Gautreau, A., Kerdelhué, B. Brain Res. Brain Res. Protoc. (1998) [Pubmed]
  31. Tachykinin NK1 receptor subtypes in the rat urinary bladder. Meini, S., Patacchini, R., Maggi, C.A. Br. J. Pharmacol. (1994) [Pubmed]
  32. Neurotensin and dopamine D2 activation oppositely regulate the same K+ conductance in rat midbrain dopaminergic neurons. Farkas, R.H., Chien, P.Y., Nakajima, S., Nakajima, Y. Neurosci. Lett. (1997) [Pubmed]
  33. [Pro9]SP and [pGlu6, Pro9]SP(6-11) interact with two different receptors in the guinea-pig ileum as demonstrated with new SP antagonists. Chassaing, G., Lavielle, S., Brunissen, A., Carruette, A., Garret, C., Petitet, F., Saffroy, M., Beaujouan, J.C., Torrens, Y., Glowinski, J. Neuropeptides (1992) [Pubmed]
  34. Reciprocal activity of longitudinal and circular muscle during intestinal peristaltic reflex. Grider, J.R. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  35. Potentiation of tachykinin-induced plasma protein extravasation by calcitonin gene-related peptide. Gamse, R., Saria, A. Eur. J. Pharmacol. (1985) [Pubmed]
  36. Effect of post-mortem delay on density of tachykinin receptors in rat peripheral tissues. Dias, L.S., Schell, D.N., Burcher, E. Peptides (1998) [Pubmed]
  37. Messenger RNA localization and further characterisation of the putative tachykinin receptor NK4 (NK3B). Donaldson, L.F., Haskell, C.A., Hanley, M.R. Recept. Channels (2001) [Pubmed]
  38. Presynaptic regulation of spinal cord tachykinin signaling via GABA(B) but not GABA(A) receptor activation. Riley, R.C., Trafton, J.A., Chi, S.I., Basbaum, A.I. Neuroscience (2001) [Pubmed]
  39. Inhibition of acid-induced hyperaemia in the rat stomach by endogenous NK2 receptor ligands. Heinemann, A., Sattler, V., Jocic, M., Holzer, P. Neurosci. Lett. (1997) [Pubmed]
  40. NK1 receptors mediate neurogenic inflammatory increase in blood flow in rat airways. Piedimonte, G., Hoffman, J.I., Husseini, W.K., Snider, R.M., Desai, M.C., Nadel, J.A. J. Appl. Physiol. (1993) [Pubmed]
  41. The expression of neuropeptides and their mRNAs in the trigeminal mesencephalic nucleus following masseteric nerve transection. Umemoto, S., Noguchi, K., Kawai, Y., Senba, E. Brain Res. Mol. Brain Res. (1994) [Pubmed]
  42. Endothelin-1 affects capsaicin-evoked release of neuropeptides from rat vas deferens. Filippelli, A., Falciani, M., Piucci, B., D'Amico, M., D'Agostino, B., Filippelli, W., Rossi, F. Eur. J. Pharmacol. (1999) [Pubmed]
  43. Vasopressin release from the rat hypothalamo-neurohypophysial system: effects of tachykinin NK-1 and NK-2 receptors agonists and antagonists. Juszczak, M. Neuro Endocrinol. Lett. (2005) [Pubmed]
  44. Chimeric NK1 (substance P)/NK3 (neurokinin B) receptors. Identification of domains determining the binding specificity of tachykinin agonists. Gether, U., Johansen, T.E., Schwartz, T.W. J. Biol. Chem. (1993) [Pubmed]
  45. Role of protein kinase C in substance P-induced synaptic depression in the nucleus accumbens in vitro. Matowe, W.C., Ananthalakshmi, K.V., Kombian, S.B. Med. Princ. Pract. (2007) [Pubmed]
  46. Substance P depresses excitatory synaptic transmission in the nucleus accumbens through dopaminergic and purinergic mechanisms. Kombian, S.B., Ananthalakshmi, K.V., Parvathy, S.S., Matowe, W.C. J. Neurophysiol. (2003) [Pubmed]
  47. Dopamine and adenosine mediate substance P-induced depression of evoked IPSCs in the rat nucleus accumbens in vitro. Kombian, S.B., Ananthalakshmi, K.V., Parvathy, S.S., Matowe, W.C. Eur. J. Neurosci. (2003) [Pubmed]
  48. No modulatory effect of neurokinin-1 receptor antagonists on serotonin uptake in human and rat brain synaptosomes. Lieb, K., Fiebich, B.L., Herpfer, I., Mantovani, M., Löffler, M., Feuerstein, T.J. Eur. Neuropsychopharmacol. (2005) [Pubmed]
  49. Increased expression of preprotachykinin, calcitonin gene-related peptide, but not vasoactive intestinal peptide messenger RNA in dorsal root ganglia during the development of adjuvant monoarthritis in the rat. Donaldson, L.F., Harmar, A.J., McQueen, D.S., Seckl, J.R. Brain Res. Mol. Brain Res. (1992) [Pubmed]
  50. Autoradiographic localization and characterization of tachykinin receptor binding sites in the rat brain and peripheral tissues. Mantyh, P.W., Gates, T., Mantyh, C.R., Maggio, J.E. J. Neurosci. (1989) [Pubmed]
  51. Functional expression of the tachykinin NK1 receptor by floor plate cells in the embryonic rat spinal cord and brainstem. Heath, M.J., Lints, T.J., Lee, C.J., Dodd, J. J. Physiol. (Lond.) (1995) [Pubmed]
  52. Effect of thiorphan on tachykinin-induced potentiation of nerve-mediated contractions of the rat isolated vas deferens. Patacchini, R., Maggi, C.A., Rovero, P., Regoli, D., Drapeau, G., Meli, A. J. Pharmacol. Exp. Ther. (1989) [Pubmed]
  53. Role of tachykinin NK receptors on the local and remote injuries following ischaemia and reperfusion of the superior mesenteric artery in the rat. Souza, D.G., Mendonça, V.A., de A Castro, M.S., Poole, S., Teixeira, M.M. Br. J. Pharmacol. (2002) [Pubmed]
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