The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

Substance P     (2S)-2-[[(2S)-1-[(2S)-6- amino-2-[[(2S)-1...

Synonyms: CHEMBL235363, CCRIS 7229, CHEBI:500492, AC1Q5IQE, DNC009207, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Substance P

  • CP-96,345, a specific non-peptide NK-1R antagonist, inhibited SP-induced rise of [Ca(2+)](i) in the astroglioma cells [1].
  • Substance P (SP), a putative nociceptive transmitter, is increased in the CSF of patients with fibromyalgia syndrome (FMS) [2].
  • 5. The results suggest (1) that ECT evokes ocular inflammation through antidromic C-fibre activation; (2) that SP contributes to the ECT-evoked miosis; and (3) that NO contributes to the antidromic C-fibre activation and possibly to the vascular responses mediated by the C-fibre transmitters [3].
  • Inhibition by nociceptin of neurogenic inflammation and the release of SP and CGRP from sensory nerve terminals [4].
  • 5. Capsaicin evoked SP release was increased in tissue taken from Crohn's disease but not ulcerative colitis patients [5].

High impact information on Substance P

  • Thus, the behavioral manifestations of threshold changes in nociceptive processing in the setting of injury do not appear to require SP or NKA [6].
  • We conclude that NO promotes cell proliferation and uPA upregulation in CVECs by inducing endogenous bFGF and that this pathway mediates the angiogenetic response to the vasoactive neuropeptide SP [7].
  • SP-induced upregulation of bFGF was prevented by the NO synthase inhibitor N omega-monomethyl-L-arginine [7].
  • Because earlier observations indicated that only nociceptive dorsal horn neurons respond to substance P (SP), we examined which morphological types of lamina I neurons express receptors for SP (NK-1r) [8].
  • Here, we report that in peripheral sensory neurons from embryonic chick dorsal root ganglia (DRG), the G protein-mediated inhibition of voltage-dependent calcium channels may best explain how norepinephrine (NE) and GABA inhibit the electrically evoked, calcium-dependent release of substance P (SP) [9].

Chemical compound and disease context of Substance P

  • This study is aimed to investigate the relationship between plasma concentrations of nitrite and nitrate as a measure of ongoing nitric oxide (NO) production, the vasodilatory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP), endotoxemia and hemodynamic changes in human septic shock [10].
  • Serotonin (5-HT) and substance P (SP) were assayed in peripheral blood in patients with known midgut carcinoids and hepatic metastases [11].
  • CONCLUSIONS: These results support the involvement of BKB1-R in the development of diabetic hyperalgesia in STZ-mice through activation of the NO, SP and CGRP pathways [12].

Biological context of Substance P

  • ACh-, Bk-, and SP-elicited choroidal vasorelaxation was greater in saline-treated newborn than juvenile pigs [13].
  • At the same dose, SP and NKA were more potent than [MePhe7]NKB in increasing MAP and HR, but did not produce water intake or wet dog shake behaviours [14].
  • On the other hand, there was no noticeable change in gene expression and immunoreactivity of SP and CGRP [15].
  • In contrast, SP, classic selective NK1 agonists, and antagonists had a high affinity for both types of binding sites [16].
  • Substance P (SP) has been shown to stimulate the hydrolysis of inositol phospholipids in peripheral tissues and in the brain [17].

Anatomical context of Substance P

  • Colocalization of NOS with VIP but not with SP was frequent in these nerve fibers [18].
  • In epithelium, SP alone elicited a significant phosphoinositide breakdown, suggesting that epithelial receptors to tachykinins may be of the NK1 subtype [19].
  • Thus, this study compared diameter responses to acetylcholine (ACH), bradykinin (BKN), and substance P (SP) between coronary microvessels (i.d.=106+/-4 microm) dissected from left ventricles of normotensive and hypertensive Dahl rats (Dahl-NT and Dahl-HT, respectively) [20].
  • 2. Anatomical investigations were performed by injecting guinea-pig airways with the neuronal tracer Fast Blue. The animals were killed 7 days later, and the ganglia were removed and immunostained with antisera against substance P (SP) and neurofilament protein (NF) [21].
  • SP-like immunoreactivity has been detected in nerve terminals innervating the adrenal medulla; however, little is known of the presence of other tachykinins in this tissue [22].

Associations of Substance P with other chemical compounds

  • The results show that both NKA- and SP-like immunoreactivities are present in the adrenal medulla [22].
  • Exposure to capsaicin produced simultaneous release of SP- and tachykinin-like immunoreactivity both in presence and absence of mucosa [23].
  • Examination of consecutive sections immunostained for NT, enkephalin (Enk), GABA, and substance P (SP) revealed that 50% of neurons with NT-LI in the caudate nucleus and nucleus accumbens exhibited Enk-LI, 15% showed GABA-LI, and 5% manifested both Enk-LI and GABA-LI; no NT-positive neurons in the striatum and nucleus accumbens showed SP-LI [24].
  • alpha-Bungarotoxin (alpha Bgt) was shown to inhibit the binding of the 125I-labeled substance P (SP) and eledoisin (EL) to the rat brain membranes with Kl values of 8.0 +/- 5.0 x 10(-8) and 1.1 +/- 0.5 x 10(-6) M, respectively [25].
  • Short-term, stress-induced CA secretion is regulated biphasically by substance P (SP) which inhibits acetylcholine (ACh) action at SP greater than 10(-6) M and facilitates CA secretion in response to metabolic and physical stressors, ACh or electrical stimulation at SP less than 10(-6) M [26].
  • The substance P receptor antagonist, CP-96,345, not only blocked AW- or PW-induced endogenous substance P expression but also abrogated AW- or PW-induced HIV replication in T cells [27].

Gene context of Substance P

  • Beyond that, CGRP was able to boost sensitization, whereas SOM and SP did not show any effects on the sensitization process [28].
  • TNFalpha attenuated SP- and NKA-induced relaxation in a time- and concentration-dependent manner, decreasing the ability of PGE(2) to relax tissues [29].
  • Culture with PGE(2) decreased SP- and PGE(2)-mediated relaxation, further implicating the activity of COX-2 in the attenuation of tachykinin signalling [29].
  • NK-1 receptor antagonists might be potent drugs for treatment of inflammatory liver disease, most likely by inhibiting SP effects [30].
  • Thus, in adult rats, the C/SMG is as susceptible as the SCG to Gu treatment; the different pattern of hyperinnervation by SP, CGRP and VIP of the C/SMG as compared with the SCG may reflect the different sources for these neuropeptides in prevertebral as compared with paravertebral ganglia [31].
  • We observed a time-dependent activation of ERK1/2, c-Jun N-terminal kinase (JNK), NFkappaB and activator protein-1 (AP-1) when pancreatic acini were stimulated with substance P [32].

Analytical, diagnostic and therapeutic context of Substance P

  • NaNp and SP induced bFGF expression as measured by Western blot analysis of CVEC extracts and by differential reverse transcriptase-polymerase chain reaction of bFGF mRNA [7].
  • The shift of the DRC for SP seen in response to vagotomy was only slightly reduced by capsaicin pretreatment [33].
  • 4. Prevertebral ganglionectomy had no significant effect on the DRCs for SP and NKA, whereas vagotomy shifted the DRCs for all three test substances to the left [33].
  • Adrenalectomy increased the content of VIP (35.4 +/- 4.0 (S.E.M.) vs control 11.9 +/- 1.1 pmol/g wet weight) but decreased that of SP (18.8 +/- 2.3 vs control 36.7 +/- 3.5 pmol/g wet weight) [34].
  • Four weeks after transplantation, TH-immunoreactive fibers were distributed in the piloerector muscles, whereas SP- and CGRP-immunoreactive fibers were present around the hair follicles [35].


  1. Interleukin-1beta upregulates functional expression of neurokinin-1 receptor (NK-1R) via NF-kappaB in astrocytes. Guo, C.J., Douglas, S.D., Gao, Z., Wolf, B.A., Grinspan, J., Lai, J.P., Riedel, E., Ho, W.Z. Glia (2004) [Pubmed]
  2. Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways. Larson, A.A., Giovengo, S.L., Russell, I.J., Michalek, J.E. Pain (2000) [Pubmed]
  3. Ocular inflammation induced by electroconvulsive treatment: contribution of nitric oxide and neuropeptides mobilized from C-fibres. Wang, Z.Y., Waldeck, K., Grundemar, L., Håkanson, R. Br. J. Pharmacol. (1997) [Pubmed]
  4. Inhibition by nociceptin of neurogenic inflammation and the release of SP and CGRP from sensory nerve terminals. Helyes, Z., Németh, J., Pintér, E., Szolcsányi, J. Br. J. Pharmacol. (1997) [Pubmed]
  5. Human colonic anti-secretory activity of the potent NK(1) antagonist, SR140333: assessment of potential anti-diarrhoeal activity in food allergy and inflammatory bowel disease. Moriarty, D., Goldhill, J., Selve, N., O'Donoghue, D.P., Baird, A.W. Br. J. Pharmacol. (2001) [Pubmed]
  6. Distinct neurochemical features of acute and persistent pain. Basbaum, A.I. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  7. Nitric oxide promotes proliferation and plasminogen activator production by coronary venular endothelium through endogenous bFGF. Ziche, M., Parenti, A., Ledda, F., Dell'Era, P., Granger, H.J., Maggi, C.A., Presta, M. Circ. Res. (1997) [Pubmed]
  8. NK-1 receptor immunoreactivity in distinct morphological types of lamina I neurons of the primate spinal cord. Yu, X.H., Zhang, E.T., Craig, A.D., Shigemoto, R., Ribeiro-da-Silva, A., De Koninck, Y. J. Neurosci. (1999) [Pubmed]
  9. G proteins couple alpha-adrenergic and GABAb receptors to inhibition of peptide secretion from peripheral sensory neurons. Holz, G.G., Kream, R.M., Spiegel, A., Dunlap, K. J. Neurosci. (1989) [Pubmed]
  10. Relationship between circulating levels of calcitonin gene-related peptide, nitric oxide metabolites and hemodynamic changes in human septic shock. Arnalich, F., Hernanz, A., Jiménez, M., López, J., Tato, E., Vázquez, J.J., Montiel, C. Regul. Pept. (1996) [Pubmed]
  11. The pentagastrin test in the diagnosis of the carcinoid syndrome. Ahlman, H., Dahlström, A., Grönstad, K., Jaffe, B.M., Nilsson, O., Oberg, K. J. Cardiovasc. Pharmacol. (1985) [Pubmed]
  12. Pathways for the bradykinin B1 receptor-mediated diabetic hyperalgesia in mice. Gabra, B.H., Sirois, P. Inflamm. Res. (2004) [Pubmed]
  13. Regulation of endothelial nitric oxide synthase by PGD(2) in the developing choroid. Dumont, I., Hardy, P., Peri, K.G., Hou, X., Molotchnikoff, S., Varma, D.R., Chemtob, S. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  14. Functional interaction between losartan and central tachykinin NK3 receptors in the conscious rat. Picard, P., Chrétien, L., Couture, R. Br. J. Pharmacol. (1995) [Pubmed]
  15. Permanent occlusion of the middle cerebral artery upregulates expression of cytokines and neuronal nitric oxide synthase in the spinal cord and urinary bladder in the adult rat. Fu, D., Ng, Y.K., Gan, P., Ling, E.A. Neuroscience (2004) [Pubmed]
  16. Pharmacological characterization of tachykinin septide-sensitive binding sites in the rat submaxillary gland. Beaujouan, J.C., Saffroy, M., Torrens, Y., Sagan, S., Glowinski, J. Peptides (1999) [Pubmed]
  17. Effects of tachykinins on phosphoinositide metabolism in the hypothalamus: is the NK1 receptor involved? Lebrun, C.J., Wende, P., Steckelings, U., Itoi, K., Unger, T. Brain Res. (1993) [Pubmed]
  18. Nitric oxide synthase in neurons and nerve fibers of lower airways and in vagal sensory ganglia of man. Correlation with neuropeptides. Fischer, A., Hoffmann, B. Am. J. Respir. Crit. Care Med. (1996) [Pubmed]
  19. Tachykinin-induced phosphoinositide breakdown in airway smooth muscle and epithelium: relationship to contraction. Grandordy, B.M., Frossard, N., Rhoden, K.J., Barnes, P.J. Mol. Pharmacol. (1988) [Pubmed]
  20. Distinct endothelial impairment in coronary microvessels from hypertensive Dahl rats. Gauthier-Rein, K.M., Rusch, N.J. Hypertension (1998) [Pubmed]
  21. Interganglionic segregation of distinct vagal afferent fibre phenotypes in guinea-pig airways. Ricco, M.M., Kummer, W., Biglari, B., Myers, A.C., Undem, B.J. J. Physiol. (Lond.) (1996) [Pubmed]
  22. Chromatographic evidence for the presence of multiple tachykinins in the bovine adrenal medulla. Basile, S., Cheung, N.S., Livett, B.G. J. Neurochem. (1992) [Pubmed]
  23. Effect of thiorphan on the response of guinea-pig isolated urinary bladder to exogenous and endogenous tachykinins. Maggi, C.A., Astolfi, M., Santicioli, P., Tramontana, M., Leoncini, G., Geppetti, P., Giachetti, A., Meli, A. J. Urol. (1990) [Pubmed]
  24. Neurotensin in projection neurons of the striatum and nucleus accumbens, with reference to coexistence with enkephalin and GABA: an immunohistochemical study in the cat. Sugimoto, T., Mizuno, N. J. Comp. Neurol. (1987) [Pubmed]
  25. alpha-Bungarotoxin interacts with the rat brain tachykinin receptors. Utkin YuN, n.u.l.l., Lazakovich, E.M., Kasheverov, I.E., Tsetlin, V.I. FEBS Lett. (1989) [Pubmed]
  26. Peptide regulation of adrenal medullary function. Livett, B.G., Marley, P.D., Wan, D.C., Zhou, X.F. J. Neural Transm. Suppl. (1990) [Pubmed]
  27. An in vitro model of morphine withdrawal manifests the enhancing effect on human immunodeficiency virus infection of human T lymphocytes through the induction of substance P. Wang, X., Douglas, S.D., Peng, J.S., Zhou, D.J., Wan, Q., Ho, W.Z. Am. J. Pathol. (2006) [Pubmed]
  28. Neuropeptides enhance irritant and allergic contact dermatitis. Gutwald, J., Goebeler, M., Sorg, C. J. Invest. Dermatol. (1991) [Pubmed]
  29. TNF alpha reduces tachykinin, PGE2-dependent, relaxation of the cultured mouse trachea by increasing the activity of COX-2. Bachar, O., Rose, A.C., Adner, M., Wang, X., Prendergast, C.E., Kempf, A., Shankley, N.P., Cardell, L.O. Br. J. Pharmacol. (2005) [Pubmed]
  30. Neurokinin-1 receptor antagonists CP-96,345 and L-733,060 protect mice from cytokine-mediated liver injury. Bang, R., Sass, G., Kiemer, A.K., Vollmar, A.M., Neuhuber, W.L., Tiegs, G. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  31. Different reinnervation patterns in the celiac/mesenteric and superior cervical ganglia following guanethidine sympathectomy in adult rats. Benarroch, E.E., Zollman, P.J., Smithson, I.L., Schmelzer, J.D., Low, P.A. Brain Res. (1994) [Pubmed]
  32. Effect of mitogen-activated protein kinases on chemokine synthesis induced by substance P in mouse pancreatic acinar cells. Ramnath, R.D., Sun, J., Adhikari, S., Bhatia, M. J. Cell. Mol. Med. (2007) [Pubmed]
  33. Modulation of gastric contractions in response to tachykinins and bethanechol by extrinsic nerves. Holzer-Petsche, U. Br. J. Pharmacol. (1991) [Pubmed]
  34. The influence of adrenal hormone status on neuroendocrine peptides in the rat anterior pituitary gland. Jones, P.M., O'Halloran, D.J., Ghatei, M.A., Domin, J., Bloom, S.R. J. Endocrinol. (1990) [Pubmed]
  35. Target-specific innervation by autonomic and sensory nerve fibers in hairy fetal skin transplanted into the anterior eye chamber of adult rat. Katoh, N., Ueda, S., Matsumoto, Y., Kishimoto, S., Yasuno, H., Kawata, M. Cell Tissue Res. (1991) [Pubmed]
WikiGenes - Universities