Gene Symbol: Tac1
Description: tachykinin, precursor 1
Alias: PPTA3, Ppt5fl, RATPPTA3, TAC, protachykinin-1, PPT, Tachykinin (substance P, neurokinin A, neuropeptide K, neuropeptide gamma), tachykinin 1
Species: rat
Products:     Tac1

Top Publications

  1. Zhao Z, Yang Y, Walker D, Davis M. Effects of substance P in the amygdala, ventromedial hypothalamus, and periaqueductal gray on fear-potentiated startle. Neuropsychopharmacology. 2009;34:331-40 pubmed publisher
  2. Li P, Chen W, Chang L, Lin S. Substance P acts via the neurokinin receptor 1 to elicit bronchoconstriction, oxidative stress, and upregulated ICAM-1 expression after oil smoke exposure. Am J Physiol Lung Cell Mol Physiol. 2008;294:L912-20 pubmed publisher
    ..These findings suggest that SP acts via the NK-1 receptor to provoke neurogenic inflammation, oxidative stress, and ICAM-1 expression after OSE in rats. ..
  3. Cao Y, Mantyh P, Carlson E, Gillespie A, Epstein C, Basbaum A. Primary afferent tachykinins are required to experience moderate to intense pain. Nature. 1998;392:390-4 pubmed
    ..We have now disrupted the mouse preprotachykinin A gene (PPT-A), which encodes substance P and a related tachykinin, neurokinin A...
  4. Singewald N, Chicchi G, Thurner C, Tsao K, Spetea M, Schmidhammer H, et al. Modulation of basal and stress-induced amygdaloid substance P release by the potent and selective NK1 receptor antagonist L-822429. J Neurochem. 2008;106:2476-88 pubmed publisher
  5. Carter M, Krause J. Structure, expression, and some regulatory mechanisms of the rat preprotachykinin gene encoding substance P, neurokinin A, neuropeptide K, and neuropeptide gamma. J Neurosci. 1990;10:2203-14 pubmed
    The rat preprotachykinin (PPT) gene encoding the neuropeptides substance P (SP), neurokinin A (NKA), neuropeptide K (NPK), and neuropeptide gamma was isolated from a lambda Charon 4A genomic library...
  6. Turner D, Martin P, Rao J, Greenspon J, Zou T, Bass B, et al. Substance P regulates migration in rat intestinal epithelial cells. Ann Surg. 2007;245:408-14 pubmed
    ..These results indicate that SP stimulates intestinal epithelial migration and increases in calcium concentration. These data support a beneficial role for SP in the maintenance of intestinal mucosal homeostasis. ..
  7. Mak I, Kramer J, Chmielinska J, Khalid M, Landgraf K, Weglicki W. Inhibition of neutral endopeptidase potentiates neutrophil activation during Mg-deficiency in the rat. Inflamm Res. 2008;57:300-5 pubmed publisher
    ..02); PR or MgD alone only reduced this activity 26% and 15%, respectively. We conclude that NEP inhibition potentiates SP-mediated neutrophil .O(2-) production and may promote other inflammatory activities during MgD. ..
  8. Kertes E, László K, Berta B, Lenard L. Effects of substance P microinjections into the globus pallidus and central nucleus of amygdala on passive avoidance learning in rats. Behav Brain Res. 2009;198:397-403 pubmed publisher
    ..Our results are the first to demonstrate that SP plays important roles, though in different ways, in learning and memory processes related to the GP and AMY. ..
  9. Li Y, Shi B, Wang D, Wang P, Laudon V, Zhang J, et al. Nerve growth factor and substance P: expression in a rat model of diabetic bladder. Int Urol Nephrol. 2011;43:109-16 pubmed publisher
    ..05). Our findings indicated that the decrease in NGF and SP may be a contributory factor in diabetic cystopathy. In addition, P. africanum could significantly upregulate the expression of NGF and SP in diabetic rats. ..

More Information


  1. Hay C, Shanley L, Davidson S, Cowie P, Lear M, McGuffin P, et al. Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones. Psychoneuroendocrinology. 2014;47:43-55 pubmed publisher
    Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents...
  2. Chu H, Kraft M, Krause J, Rex M, Martin R. Substance P and its receptor neurokinin 1 expression in asthmatic airways. J Allergy Clin Immunol. 2000;106:713-22 pubmed
    ..Antibiotic intervention may be effective in the treatment of asthma partly through the downregulation of the neurogenic process. ..
  3. Wang H, Deng Y, Reiner A. In situ hybridization histochemical and immunohistochemical evidence that striatal projection neurons co-containing substance P and enkephalin are overrepresented in the striosomal compartment of striatum in rats. Neurosci Lett. 2007;425:195-9 pubmed
  4. Ding X, Ardell J, Hua F, McAuley R, Sutherly K, Daniel J, et al. Modulation of cardiac ischemia-sensitive afferent neuron signaling by preemptive C2 spinal cord stimulation: effect on substance P release from rat spinal cord. Am J Physiol Regul Integr Comp Physiol. 2008;294:R93-101 pubmed
    ..These results suggest that preemptive SCS from the high cervical region modulates sensory afferent signaling from the ischemic myocardium. ..
  5. Shang J, Yuan J, Xu H, Tang R, Dong Y, Xie J. Shugan-decoction relieves visceral hyperalgesia and reduces TRPV1 and SP colon expression. World J Gastroenterol. 2013;19:8071-7 pubmed publisher
    ..AWR) to colorectal balloon-induced distension (at 5 mmHg increments) to determine the pain pressure threshold (PPT, evidenced by pain behavior)...
  6. Kobayashi Y, Sekiguchi M, Konno S, Kikuchi S. Increased intramuscular pressure in lumbar paraspinal muscles and low back pain: model development and expression of substance P in the dorsal root ganglion. Spine (Phila Pa 1976). 2010;35:1423-8 pubmed publisher
    ..These findings suggest that IMP and decreased IMBF in the lumbar paraspinal muscles induce inflammation and pain in the lower back. ..
  7. Lallemend F, Lefebvre P, Hans G, Rigo J, Van De Water T, Moonen G, et al. Substance P protects spiral ganglion neurons from apoptosis via PKC-Ca2+-MAPK/ERK pathways. J Neurochem. 2003;87:508-21 pubmed
  8. Gibran N, Tamura R, Tsou R, Isik F. Human dermal microvascular endothelial cells produce nerve growth factor: implications for wound repair. Shock. 2003;19:127-30 pubmed
    ..Our data suggest that MECs may be unrecognized contributors to nerve regeneration after cutaneous injury. ..
  9. Funakoshi K, Goris R, Kadota T, Atobe Y, Nakano M, Kishida R. Prenatal development of peptidergic primary afferent projections to mouse lumbosacral autonomic preganglionic cell columns. Brain Res Dev Brain Res. 2003;144:107-19 pubmed
    ..The potential direct connections between the peptidergic primary sensory fibers and preganglionic neurons innervating the pelvic viscera might provide a circuit for spinal visceral reflexes active in embryos. ..
  10. Azzolina A, Bongiovanni A, Lampiasi N. Substance P induces TNF-alpha and IL-6 production through NF kappa B in peritoneal mast cells. Biochim Biophys Acta. 2003;1643:75-83 pubmed
    ..These findings indicate that the NF kappa B pathway is involved in the transcriptional regulation of the TNF-alpha and IL-6 overexpression in primary SP-stimulated mast cells. ..
  11. Camargo E, Ferreira T, Ribela M, De Nucci G, Landucci E, Antunes E. Role of substance P and bradykinin in acute pancreatitis induced by secretory phospholipase A2. Pancreas. 2008;37:50-5 pubmed publisher
    ..We concluded that NK-1 and B2 receptors can regulate important steps in the local and remote inflammation during acute pancreatitis induced by sPLA2. ..
  12. Liu Z, Liu H, Yang X, Xu X, Zhang W, Li Z. Effects of insulin-like growth factor-1 on expression of sensory neuropeptides in cultured dorsal root ganglion neurons in the absence or presence of glutamate. Int J Neurosci. 2010;120:698-702 pubmed publisher
    ..The expression of SP and CGRP increased significantly in primary cultured DRG neurons in the presence of IGF-1. The ability of IGF-1 on SP and CGRP expression may play a role in neurogenic inflammation or nociception. ..
  13. Caudle R, Mannes A, Keller J, Perez F, Suckow S, Neubert J. Sensitization of spinal cord nociceptive neurons with a conjugate of substance P and cholera toxin. BMC Neurosci. 2007;8:30 pubmed
    ..Furthermore, these results demonstrate that SP-CTA can be used as a tool to study sensitization of central neurons in vivo in the absence of an injury. ..
  14. Kido M, Ibuki T, Danjo A, Kondo T, Zhang J, Yamaza T, et al. Immunocytochemical localization of the neurokinin 1 receptor in rat dental pulp. Arch Histol Cytol. 2005;68:259-65 pubmed
  15. Brady F, Bakhle Y, Bell C. Evaluation of the involvement of nitric oxide and substance P in reducing baroreflex gain in the genetically hypertensive (GH) rat. Acta Physiol Hung. 2002;89:451-61 pubmed
    ..Nitric oxide, but not substance P, appears to play an inhibitory role in the rat arterial baroreflex. Impairment of baroreflex gain in GH rats is not secondary to altered nitric oxide signaling. ..
  16. Chen K, Lai Y, Chen M. Oxygen radicals and substance P in perinatal hypoxia-exaggerated, monocrotaline-induced pulmonary hypertension. Chin J Physiol. 2012;55:82-90 pubmed publisher
    ..These results suggest that both ROS and substance P are involved in perinatal hypoxia-augmented, MCT-induced pulmonary hypertension. ..
  17. Nagashima A, Takano Y, Tateishi K, Matsuoka Y, Hamaoka T, Kamiya H. Cardiovascular roles of tachykinin peptides in the nucleus tractus solitarii of rats. Brain Res. 1989;487:392-6 pubmed
    ..These results indicate that NKB may also be a neuromodulator on cardiovascular responses in the NTS. ..
  18. Hou L, Tang H, Chen Y, Wang L, Zhou X, Rong W, et al. Presynaptic modulation of tonic and respiratory inputs to cardiovagal motoneurons by substance P. Brain Res. 2009;1284:31-40 pubmed publisher
  19. Nakatsuka T, Chen M, Takeda D, King C, Ling J, Xing H, et al. Substance P-driven feed-forward inhibitory activity in the mammalian spinal cord. Mol Pain. 2005;1:20 pubmed
    ..Our findings reveal a fundamental role of SP in recruiting inhibitory activity for sensory processing, which may have important therapeutic implications in treating pathological pain conditions using SP receptors as targets. ..
  20. Fernandez C, Debeljuk L, Diaz E, Diaz B. Age differences in neurokinin A and substance P from the hypothalamus, pituitary, pineal gland, and striatum of the rat. Effect of exogenous melatonin. Peptides. 2002;23:941-5 pubmed
    ..Our results indicate that melatonin may regulate tachykinin stores during aging mainly on structures of the neuroendocrine-reproductive axis. ..
  21. Amantini C, Mosca M, Lucciarini R, Perfumi M, Santoni G. Thiorphan-induced survival and proliferation of rat thymocytes by activation of Akt/survivin pathway and inhibition of caspase-3 activity. J Pharmacol Exp Ther. 2008;327:215-25 pubmed publisher
    ..thiorphan, a specific NEP/CD10 inhibitor, by means of miniosmotic pumps, enhanced rat thymocyte preprotachykinin-A (PPT-A) and NK(1)R mRNA expression as well as SP and NK(1)R protein levels in an NK(1)R-dependent manner...
  22. Cattaruzza F, Cottrell G, Vaksman N, Bunnett N. Endothelin-converting enzyme 1 promotes re-sensitization of neurokinin 1 receptor-dependent neurogenic inflammation. Br J Pharmacol. 2009;156:730-9 pubmed publisher
    ..We investigated whether ECE-1 regulates NK(1) receptor re-sensitization and the pro-inflammatory effects of SP in the endothelium...
  23. Imamura T, Ishizuka O, Zhong C, Ogawa T, Nakayama T, Kurizaki Y, et al. An extract (THC-002) of Ba-Wei-Die-Huang-Wan inhibits expression of tachykinins, and P2X3 and TRPV1 receptors, and inhibits ATP-induced detrusor overactivity in spontaneously hypertensive rats. Neurourol Urodyn. 2009;28:529-34 pubmed publisher
    ..In SHRs, THC-002 reduced the bladder expression of tachykinins and P2X3 and TRPV1 receptors, and inhibited ATP-induced detrusor overactivity. These effects may explain part of its beneficial effects on LUTS. ..
  24. Commons K. Locally collateralizing glutamate neurons in the dorsal raphe nucleus responsive to substance P contain vesicular glutamate transporter 3 (VGLUT3). J Chem Neuroanat. 2009;38:273-81 pubmed publisher
    ..Taken together, these findings indicate locally collateralizing glutamate neurons responsive to substance P contain VGLUT3. ..
  25. Chen W, Zhang X, Lu Z, Wei D. [Effect of triptolide on iNOS and SP expressions in spinal dorsal horn and dorsal root ganglion of rats with adjuvant arthritis]. Zhongguo Zhong Yao Za Zhi. 2014;39:1675-9 pubmed
    ..TP shows a good analgesic effect on AA, and could inhibit the iNOS and SP expressions in spinal dorsal horn and DRG in rats with adjuvant arthritis, which may be one of action mechanisms for the analgesic effect of TP. ..
  26. Zhang J, Guo Z. [Changes in substance P in myocardium and dorsal root ganglion following coronary artery occlusion in rats]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2006;18:201-5 pubmed
  27. Barry C, Helps S, den Heuvel C, Vink R. Characterizing the role of the neuropeptide substance P in experimental subarachnoid hemorrhage. Brain Res. 2011;1389:143-51 pubmed publisher
    ..Blockade of SP did not improve any outcome parameters, suggesting that neurogenic inflammation may be less critical than other factors in these models. ..
  28. Hua F, Ricketts B, Reifsteck A, Ardell J, Williams C. Myocardial ischemia induces the release of substance P from cardiac afferent neurons in rat thoracic spinal cord. Am J Physiol Heart Circ Physiol. 2004;286:H1654-64 pubmed
  29. Cardenas A, Lowe R, Oh S, Bodkin S, Kenney T, LaMorte W, et al. Hemodynamic effects of substance P and its receptor antagonist RP67580 in anesthetized rats with carbon tetrachloride-induced cirrhosis. Scand J Gastroenterol. 2008;43:328-33 pubmed
    ..RP687580 decreases PP and reduces SP-induced hypotension in cirrhotic rats. NO blockade abolishes the effect of SP on PP. SP contributes to splanchnic vasodilatation in cirrhosis and this effect may be mediated by NO. ..
  30. Reed K, Fruin A, Bishop Bartolomei K, Gower A, Nicolaou M, Stucchi A, et al. Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation. J Surg Res. 2002;108:165-72 pubmed
  31. Zhang G, Chen W, Lao L, Marvizon J. Cannabinoid CB1 receptor facilitation of substance P release in the rat spinal cord, measured as neurokinin 1 receptor internalization. Eur J Neurosci. 2010;31:225-37 pubmed publisher
    ..This results in a pronociceptive effect of CB1 receptors in the spinal cord. ..
  32. Lacoste B, Riad M, Ratté M, Boye S, Levesque D, Descarries L. Trafficking of neurokinin-1 receptors in serotonin neurons is controlled by substance P within the rat dorsal raphe nucleus. Eur J Neurosci. 2009;29:2303-14 pubmed publisher
    ..These results suggest that the trafficking of NK1rs represents a cellular mechanism in control of the modulation of serotonin neuron activity by SP in DRN. ..
  33. Zhang W, Li H, Xing Z, Yuan H, Kindy M, Li Z. Expression of mRNAs for PPT, CGRP, NF-200, and MAP-2 in cocultures of dissociated DRG neurons and skeletal muscle cells in administration of NGF or NT-3. Folia Histochem Cytobiol. 2012;50:312-8 pubmed
    ..known about the association of target SKM cells with distinct NTs on the expression of mRNAs for preprotachykinin (PPT), calcitonin-gene related peptide (CGRP), neurofilament 200 (NF-200), and microtubule associated protein 2 (MAP-2) ..
  34. Wallin J, Schott E. Substance P release in the spinal dorsal horn following peripheral nerve injury. Neuropeptides. 2002;36:252-6 pubmed
    ..This change in SP release may reflect an altered sensory processing or may instead relate to adaptive responses to promote recovery. ..
  35. Li L, Qu R, Wang W, Guo H. Significance of changes of gastrointestinal peptides in blood and ileum of experimental spleen deficiency rats. World J Gastroenterol. 2003;9:553-6 pubmed
    ..the Chinese herbs (Jiawei Sijun zi Tang) currently used have partially therapeutic effect. ..
  36. Schelegle E, Walby W, Alfaro M, Wong V, Putney L, Stovall M, et al. Repeated episodes of ozone inhalation attenuates airway injury/repair and release of substance P, but not adaptation. Toxicol Appl Pharmacol. 2003;186:127-42 pubmed
    ..This depressed cell proliferative response may be in part the result of diminished neutrophil inflammation and/or release of mitogenic neuropeptides in response to ozone-induced injury. ..
  37. Min M, Wu Y, Shih P, Lu H, Lin C, Wu Y, et al. Physiological and morphological properties of, and effect of substance P on, neurons in the A7 catecholamine cell group in rats. Neuroscience. 2008;153:1020-33 pubmed publisher
    ..These results provide the first description of the intrinsic regulation of membrane properties of, and the excitatory effect of Sub-P on, A7 area neurons, which play an important role in pain regulation. ..
  38. Juszczak M, Boczek Leszczyk E, Stempniak B. Effect of melatonin on the vasopressin secretion as influenced by tachykinin NK-1 receptor agonist and antagonist: in vivo and in vitro studies. J Physiol Pharmacol. 2007;58:829-43 pubmed
    ..They have also shown that, under present experimental conditions, the stimulatory effect of NK-1 receptor activation on AVP secretion into the blood is sensitive to inhibitory influence of melatonin. ..
  39. Wang Y, Novotny M, Quaiserová Mocko V, Swain G, Wang D. TRPV1-mediated protection against endotoxin-induced hypotension and mortality in rats. Am J Physiol Regul Integr Comp Physiol. 2008;294:R1517-23 pubmed publisher
  40. Wei T, Li W, Guo T, Zhao R, Wang L, Clark D, et al. Post-junctional facilitation of Substance P signaling in a tibia fracture rat model of complex regional pain syndrome type I. Pain. 2009;144:278-86 pubmed publisher
    ..We postulate that SP activation of these up-regulated NK1 receptors results in skin warmth, protein leakage, edema, and keratinocyte proliferation in the injured limb. ..
  41. Zhang X, Douglas K, Jin H, Eldaif B, Nassar R, Fraser M, et al. Sprouting of substance P-expressing primary afferent central terminals and spinal micturition reflex NK1 receptor dependence after spinal cord injury. Am J Physiol Regul Integr Comp Physiol. 2008;295:R2084-96 pubmed publisher
    ..These experiments show that tachykinin action at spinal NK1 receptors plays a major role in the spinal micturition reflex in SCI rats. ..
  42. Yamauchi K, Inoue G, Koshi T, Yamashita M, Ito T, Suzuki M, et al. Nerve growth factor of cultured medium extracted from human degenerative nucleus pulposus promotes sensory nerve growth and induces substance p in vitro. Spine (Phila Pa 1976). 2009;34:2263-9 pubmed publisher
    ..These in vitro results may suggest that NGF from the NP promotes the growth of sensory nerve fibers innervating the degenerated intervertebral disc and may induce SP related with pain transmission. ..
  43. Hannibal J, Fahrenkrug J. Immunoreactive substance P is not part of the retinohypothalamic tract in the rat. Cell Tissue Res. 2002;309:293-9 pubmed
  44. Inoue A, Ohnishi M, Fukutomi C, Kanoh M, Miyauchi M, Takata T, et al. Protein kinase A-dependent substance P expression by pituitary adenylate cyclase-activating polypeptide in rat sensory neuronal cell line ND7/23 cells. J Mol Neurosci. 2012;48:541-9 pubmed
    ..increase in the number of neurite-bearing cells and the expression of the substance P precursor (PPT) mRNA in 24 h...
  45. Steagall R, Sipe A, Williams C, Joyner W, Singh K. Substance P release in response to cardiac ischemia from rat thoracic spinal dorsal horn is mediated by TRPV1. Neuroscience. 2012;214:106-19 pubmed publisher
    ..These results suggest that spinal release of the putative nociceptive transmitter SP occurs, at least in part, via a TRPV1 mechanism. ..
  46. Carthew H, Ziebell J, Vink R. Substance P-induced changes in cell genesis following diffuse traumatic brain injury. Neuroscience. 2012;214:78-83 pubmed publisher
    ..These results suggest that NAT treatment results in neuroprotection following TBI, mediated in part via inhibition of microglia. ..
  47. Chapman K, Lyons V, Harmar A. The sequence of 5' flanking DNA from the rat preprotachykinin gene; analysis of putative transcription factor binding sites. Biochim Biophys Acta. 1993;1172:361-3 pubmed
    ..The sequenced region encodes a number of putative transcription factor binding sites which may play important roles in the regulation of rPPT-A gene transcription. ..
  48. Mukda S, Møller M, Ebadi M, Govitrapong P. The modulatory effect of substance P on rat pineal norepinephrine release and melatonin secretion. Neurosci Lett. 2009;461:258-61 pubmed publisher
    ..However, in the presence of NE, substance P inhibited the NE-induced increase in AANAT activity and melatonin secretion. This is the first time that a function for substance P in the mammalian pineal gland has been demonstrated. ..
  49. Kombian S, Ananthalakshmi K, Parvathy S, Matowe W. Substance P depresses excitatory synaptic transmission in the nucleus accumbens through dopaminergic and purinergic mechanisms. J Neurophysiol. 2003;89:728-37 pubmed
    ..Since the cellular and synaptic effects of SP resemble those of cocaine and amphetamine, it may serve as an endogenous psychogenic peptide. ..
  50. Greenwell T, Martin Schild S, Inglis F, Zadina J. Colocalization and shared distribution of endomorphins with substance P, calcitonin gene-related peptide, gamma-aminobutyric acid, and the mu opioid receptor. J Comp Neurol. 2007;503:319-33 pubmed
    ..Several areas in which EM1 and EM2 showed extensive shared distributions, but no detectable colocalization with other signaling molecules, are also described. ..
  51. Pan P, Huang S, Hu C. Nerve growth factor induced expression of iNOS and substance P in dorsal root ganglion sensory neuron and interferon regulatory factor-1. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011;36:386-91 pubmed publisher
    ..IRF-1 may be a therapeutic target for airway neurogenic inflammation. ..
  52. Hughes D, Scott D, Riddell J, Todd A. Upregulation of substance P in low-threshold myelinated afferents is not required for tactile allodynia in the chronic constriction injury and spinal nerve ligation models. J Neurosci. 2007;27:2035-44 pubmed
    ..They also suggest that any release of substance P from injured Abeta afferents is unlikely to activate NK1 receptors in the dorsal horn or contribute to neuropathic pain. ..
  53. Sang Q, Young H. The origin and development of the vagal and spinal innervation of the external muscle of the mouse esophagus. Brain Res. 1998;809:253-68 pubmed