883:
the manifestation and continuation of human affective disorders. The measurement of serum peptide levels in depressed patients as well as anxious patients displayed higher plasma levels of tachykinins than their low-anxiety counterparts. In addition to studies of plasma levels of TKs, cerebrospinal fluid (CSF) levels of neurokinin A have also been directly correlated with depression. Under states of depression, neurokinin immunoreactivity is increased in the frontal cortex, and decreased in the striatum. These peptide levels were not found to be normalized by lithium treatment in mice. Elevated levels of tachykinins in CSF have been found in patients with fibromyalgia syndrome, a disorder that is strongly correlated with depression in human patients. Tachykinin ligands have been extensively studied and determined to be functionally linked to the control of affective phenotypes in a complex physiological manner.
689:
363:
InChI=1S/C50H80N14O14S/c1-26(2)18-34(45(73)58-32(42(53)70)15-17-79-6)57-38(67)23-55-49(77)40(27(3)4)63-47(75)35(19-29-12-8-7-9-13-29)60-48(76)37(24-65)62-46(74)36(21-39(68)69)61-50(78)41(28(5)66)64-44(72)33(14-10-11-16-51)59-43(71)31(52)20-30-22-54-25-56-30/h7-9,12-13,22,25-28,31-37,40-41,65-66H,10-11,14-21,23-24,51-52H2,1-6H3,(H2,53,70)(H,54,56)(H,55,77)(H,57,67)(H,58,73)(H,59,71)(H,60,76)(H,61,78)(H,62,74)(H,63,75)(H,64,72)(H,68,69)/t28-,31+,32+,33+,34+,35+,36+,37+,40+,41+/m1/s1
814:
373:
InChI=1/C50H80N14O14S/c1-26(2)18-34(45(73)58-32(42(53)70)15-17-79-6)57-38(67)23-55-49(77)40(27(3)4)63-47(75)35(19-29-12-8-7-9-13-29)60-48(76)37(24-65)62-46(74)36(21-39(68)69)61-50(78)41(28(5)66)64-44(72)33(14-10-11-16-51)59-43(71)31(52)20-30-22-54-25-56-30/h7-9,12-13,22,25-28,31-37,40-41,65-66H,10-11,14-21,23-24,51-52H2,1-6H3,(H2,53,70)(H,54,56)(H,55,77)(H,57,67)(H,58,73)(H,59,71)(H,60,76)(H,61,78)(H,62,74)(H,63,75)(H,64,72)(H,68,69)/t28-,31+,32+,33+,34+,35+,36+,37+,40+,41+/m1/s1
239:
571:
680:
nerves are abundant in coronary arteries and in the cardiac ganglia. The diverse responses that are triggered by locally released tachykinins produce beneficial effects such as modulation of ganglion transmission. However, it is also possible that excessive stimulation of cardiac afferents and release of tachykinins, during pathological conditions such as myocardial infarction, could contribute to certain human pathologies.
192:
524:. Both substance P and neurokinin A are encoded by the same mRNA, which when alternatively spliced can be translated into either compound. It has various roles in the body of humans and other animals, specifically stimulation of extravascular smooth muscle, vasodilation, hypertensive action, immune system activation, and pain management. The deduced amino acid sequence of neurokinin A is as follows:
28:
713:(NK3R). Neurokinin A binds to the G-protein coupled receptor ultimately increasing the release of inositol-phosphate and calcium second messengers. Each receptor demonstrates a specific affinity for either neurokinin A or substance P peptides. Both peptides, however, can act as full agonists on either receptor, although their potency is decreased when not bound to their specific receptor.
460:
866:
examined the role tachykinins play in bronchoconstriction, most notably through the receptor NK2, though regulation of NK2 receptors seems to be mediated by the activity of NK1 receptors eluting to complicated inhibition mechanism. Administration of DNK333 (a dual tachykinin receptor NK1/NK2 antagonist) have shown protective activity against neurokinin A induced bronchoconstriction.
629:
activated within nerve tissue in response to damage in order to protect cellular, protein, and nucleic acid integrity. A large variety of neuroprotective signaling mechanisms exist, which can be manipulated by drugs to reduce damage from cellular damage in neurons. Tachykinins thus have a number of neuroprotective physiological roles in medical conditions
617:
that tachykinins are a major component of the neural inflammatory response at peripheral tissues as well as the CNS. The ability to regulate tachykinin secretion represents an important mechanism for designing potentially useful drugs to treat inflammation. Neurokinin A has been associated with the chemokines
891:
Epilepsy is a broad category of disorders with varying types of severity and presented symptoms. Neurokinins have been experimentally determined as possible predictor in the generation of certain forms of epilepsy. Experimentally when substance P is injected into the rat hippocampus, it significantly
882:
Affective disorders are characterized by a frequent, fluctuating alteration in mood, affecting the patient's thoughts, emotions, and behaviors. Affective disorders include depression, anxiety, and bipolar disorder. A number of approaches have been utilized to study the role that neurokinin A plays in
650:
into and within the extravascular space. Since lymphocytes must be positioned correctly to interact with other cells, the pattern of chemokine receptors and the type and distribution of chemokines in tissues critically influence immune responses. The molecular mechanism behind neurokinin's role as a
865:
Bronchoconstriction is among the most prominent and extensively studied effects caused by tachykinins. Tachykinins have numerous effects in the respiratory systems especially in asthma patients who are more responsive to tachykinin administration. Through studies with human airways researchers have
845:
Circulating concentrations of neurokinin A is an independent indicator of poor prognosis in certain cancers such as carcinoids. Patients presenting with neurokinin A plasma concentrations of >50 pmol/L showed a poorer 3 year survival rate than patients presenting with neurokinin A concentrations
628:
Neuronal tissue can be severely damaged either through physical trauma or intracellular stresses, either chronic or acute. Either of these scenarios can result in calcium overload, protein degradation, the unfolded protein response or an accumulation of DNA damage. Endogenous cellular responses are
679:
Neurokinin has been shown to contribute to both bradycardia and myocardial infarctions through the activation of NK2 receptors. The dual sensory-motor function of neurokinin A containing afferent neurons is a component of the intracardiac nervous system. Varicose processes of tachykinin-containing
853:
disease (MGC) commonly receive neurokinin A test to determine the progression of their disease. Midgut
Carcinoid disease is an uncommon disease with occurrence rates of approximately 1.4 per 100,000 of the population per year. MGC has an unpredictable disease progression depending on the patient,
616:
Inflammatory responses within the central nervous system (CNS) are often the result of traumatic injury or exposure to infectious agents. Inflammation provides a protective immune response to such stresses may also result in progressive damage to the CNS. There is significant evidence to indicate
754:. The amino acid sequence of substance P and neurokinin A are well conserved across mammals species. Structure of mammalian neurokinin A was obtained using CD spectropolarimetry and 2D proton NMR. Analysis showed that in water, the peptide adopts an extended conformation while in the presence of
721:
NK-2 receptors are expressed predominantly in the CNS. Networks involved in emotional processing, such as the prefrontal cortex, cingulate cortex, and amygdala, show the highest concentration of NK-2 receptors. NK-2 receptor antagonists have been theorized to have antidepressant benefits and are
515:
processing, satiety, and smooth muscle contraction. Tachykinins are known to be highly excitatory neurotransmitters in major central neural systems. Neurokinin A is ubiquitous in both the central and peripheral mammalian nervous systems, and seems to be involved in reactions to pain and the
733:
has been demonstrated to be a potent, selective and competitive antagonist of tachykinin NK2 receptors, both in animal and human models. In vivo animal models, MEN 11420 produces an effective and long-lasting blockade of the NK2 receptors expressed in the smooth muscle of the intestinal,
612:
system may be under the control of both endogenously released corticotropin-releasing hormone and SP and neurokinin A. This study directly links the secretion of neurokinin A and SP to certain forms of depression characterized by the corticoid receptor hypothesis of depression.
577:
Modified from: Sun J, Ramnath RD, Tamizhselvi R, Bhatia M."Neurokinin A engages neurokinin-1 receptor to induce NF-kappaB-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways." Am J Physiol Cell
Physiol. 2008 Sep;295(3):C679-91
670:
The binding of neurokinin A to the NKR-2 results in bronchoconstriction, mucus production in the lungs and process neurogenic inflammation. This release is propagated through the stimulation of e-NANC nerves in the bronchial epithelium via an axon-reflex mechanism.
499:), formerly known as Substance K, is a neurologically active peptide translated from the pre-protachykinin gene. Neurokinin A has many excitatory effects on mammalian nervous systems and is also influential on the mammalian inflammatory and pain responses.
658:, and appear to be involved in one specific receptor since the effect can be completely abolished by a NK-2 receptor-selective antagonist. The inhibitory effect of neuronkinin A is countered by the excitatory effect of a structurally similar compound:
1251:
Steinberg, R; Alonso, R; Griebel, G; Bert, L; Jung, M; Oury-Donat, F; et al. (2001). "Selective blockade of neurokinin-2 receptors produces antidepressant-like effects associated with reduced corticotropin-releasing factor function".
645:
increasing the migration into infected tissues. This migration is necessary for the pathogen seeking activity of T-cells. Some chemokines trigger the intravascular adhesion of T-cells whereas others direct the migration of
854:
symptoms and progression range from rapid and aggressive to chronic. Treatment is difficult because of the varying degrees of severity, so assessing the extent of the disease is extremely important in effective treatment.
831:
mice show normal fertility and behavioral patterns (litter-mate socialization and pup rearing), but have a reduced sense of anxiety when threatened, compared to both wild-type mice and other mouse models of depression.
722:
presently in clinical trials. As a consequence of its ability to stimulate intestinal smooth muscle, NKA is considered to be specifically active in regulating intestinal motility by its action on NK2 receptors.
1603:
Nagano, Masatoshi; Oishi, Takao; Suzuki, Hidenori (2011). "Distribution And
Pharmacological Characterization Of Primate NK-2 Tachykinin Receptor In The Central Nervous System Of The Rhesus Monkey".
641:
and white blood cells. Chemical signals therefore are an important component of paracrine, autocrine and endocrine signaling. Neurokinin A was shown to be a potent chemo attractor for
1066:
Schäffer, Dávid A.; Gábriel, Robert (2005). "Two Major
Tachykinins, Substance P And Substance K, Are Localized To Distinct Subsets Of Amacrine Cells In The Anuran Retina".
608:
from the hypothalamus, have been studied in many clinical manifestations of pathological depression. Studies have shown that stress-induced activation of the noradrenergic
1769:
JES Ardill1, BJ Johnston1, GB Turner1, A McGinty2 & DR McCance1 "Improved
Prognosis in Midgut Carcinoid patients by treating raised circulating Neurokinin A (NKA)"
1829:"Neurokinin A engages neurokinin-1 receptor to induce NF-kappaB-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways"
1210:
Burbach, Guido J; Kyu; Zivony, Adam S; Kim, Amy; Aranda, Jennifer; Wright, Stacey; Naik, Shubhada M; Caughman, S Wright; Ansel, John C; Armstrong, Cheryl A (2001).
2500:
2679:
820:
Modified from:Nakanishi, Shigetada. "Molecular
Mechanisms Of Intercellular Communication In The Hormonal And Neural Systems." IUBMB Life 58.5/6 (2006): 349-357
693:
Mechanism of neurokinin induced neurogenic inflammation. Neuropeptides are released from C-fibers due to nervous tissue stress and induce many cellular pathways
1878:
Nishimori, Toshikazu; et al. (2011). "Knockdown Of The
Tachykinin Neurokinin 1 Receptor By Intrathecal Administration Of Small Interfering RNA In Rats".
1828:
473:
1520:
Hoover, Donald B.; Chang, Yingzi; Hancock, John C. (1998). "Characterization of responses to neurokinin A in the isolated perfused guinea pig heart".
2423:
2418:
2408:
662:. The opposite effects on myelogenesis by substance P and neurokinin A may represent an important feedback mechanism for maintenance of homeostasis.
892:
lowers the initiation threshold for seizures induced in a dose-dependent manner. Experimental data thus has indicated a pro-convulsant role for the
585:. Additionally both SP neurokinin A is found in the neurosensory system and modulates a wide range of inflammatory and tissue repairing processes
68:
32:
862:
The blocking of neuropeptide signaling has come become a novel therapeutic target for suppression of bronchial constriction in asthma patients.
2453:
2714:
2699:
2842:
2837:
2599:
2493:
2373:
389:
2659:
2649:
2644:
2639:
2624:
2619:
2579:
582:
2807:
2694:
2584:
2574:
2569:
2674:
2629:
2564:
596:. Inflammation, tissue healing and cell proliferation have been linked to both SP and neurokinin A release into surrounding tissues.
846:
of less than 50 pmol/L. These types of studies show that measuring tachykinin levels in human patients may have clinical relevance.
2709:
2604:
2486:
1999:
1433:"The NK-2 Receptor Antagonist SR 48968C Does Not Improve Adenosine Hyperresponsiveness And Airway Obstruction In Allergic Asthma"
397:
C((C(=O)N(CC(=O)O)C(=O)N(CO)C(=O)N(Cc1ccccc1)C(=O)N(C(C)C)C(=O)NCC(=O)N(CC(C)C)C(=O)N(CCSC)C(=O)N)NC(=O)(CCCCN)NC(=O)(Cc2cnc2)N)O
73:
588:. In various tissues, such as the skin, the release of bioactive tachykinins by sensory nerve fibers C, that extend from the
281:
2868:
1167:
Zimmer, Andreas; et al. (2010). "Modulation Of The CRH System By
Substance P/NKA In An Animal Model Of Depression".
1109:
Severini, C; Improta, G; Falconieri-Erspamer, G; Salvadori, S; Erspamer, V (June 2002). "The tachykinin peptide family".
92:
874:
Neurokinin A is involved in many stress induced neurological disorders, such as depression, schizophrenia and epilepsy.
468:
1667:"A novel tachykinin NK2 receptor antagonist prevents motility-stimulating effects of neurokinin A in small intestine"
354:
80:
1788:
Joos, G.F.; Vincken, W.; Louis, R.; Schelfhout, V.J.; Wang, J.H.; Shaw, M.J.; Cioppa, G.D.; Pauwels, R.A. (2004).
905:
782:
genes in mice encode four very distinct peptides with varying physiological function. Alternative splicing of the
480:
2363:
1927:
Maggi C, Patacchini R, Rovero P, Giachetti A (1993). "Tachykinin receptors and tachykinin receptor antagonists".
637:
The immune system is a highly integrated system which receives input from many sources, such as sites of injury,
605:
1867:
1790:"Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients"
802:
tac1), which are further processed into several related peptides including neurokinin A and substance P. The
1212:"The Neurosensory Tachykinins Substance P and Neurokinin A Directly Induce Keratinocyte Nerve Growth Factor"
2378:
1665:
Lördal, Mikael; Navalesi, Giovanni; Theodorsson, Elvar; Maggi, Carlo A; Hellström, Per M (September 2001).
331:
298:
85:
1992:
1956:
Regoli D, Boudon A, Fauchére J (1994). "Receptors and antagonists for substance P and related peptides".
699:
1306:"The Mammalian Tachykinin Ligand-Receptor System: An Emerging Target For Central Neurological Disorders"
956:"Three-dimensional structure of the mammalian tachykinin peptide neurokinin A bound to lipid micelles"
2398:
1393:
Mackay, Ian R.; Rosen, Fred S. (2000). "T-Cell
Function and Migration — Two Sides of the Same Coin".
915:
292:
910:
604:
The overstimulation of the hypothalamic–pituitary–adrenal axis system and elevated secretion of
2448:
1985:
586:
750:
Tachykinins are a structurally related group of neuropeptides sharing the C-terminal sequence
2788:
2739:
2520:
259:
1913:
1480:
Walsh, David A.; McWilliams, Daniel F. (2006). "Tachykinins And The
Cardiovascular System".
920:
581:
Like Substance P , Neurokinin A is present in excitatory neurons and secretory cells of the
2393:
967:
340:
215:
138:
162:
8:
2509:
2250:
589:
205:
142:
1016:"Molecular Mechanisms Of Intercellular Communication In The Hormonal And Neural Systems"
971:
2512:
2082:
2057:
1940:
1859:
1740:
1715:
1691:
1666:
1628:
1573:
1556:
1462:
1330:
1305:
1192:
1134:
1091:
1045:
988:
955:
517:
1557:"Tissue Distribution And Quantitation Of The mRNAs For Three Rat Tachykinin Receptors"
979:
2873:
2087:
2026:
1965:
1944:
1895:
1851:
1811:
1745:
1696:
1620:
1578:
1537:
1533:
1497:
1454:
1449:
1432:
1410:
1375:
1335:
1261:
1233:
1228:
1211:
1184:
1126:
1083:
1037:
993:
944:
1863:
1632:
1466:
1196:
1138:
1095:
742:
Neurokinin A was isolated from porcine spinal cord in 1983 by von Euler and Gaddum.
625:, both of which are heavily involved in the inflammatory process during infections.
511:
family of neuropeptide neurotransmitters. Tachykinins are important contributors to
1936:
1887:
1843:
1801:
1735:
1731:
1727:
1686:
1678:
1646:
1612:
1568:
1529:
1489:
1444:
1402:
1367:
1325:
1317:
1223:
1176:
1118:
1075:
1049:
1027:
983:
975:
412:
133:
320:
2478:
2413:
2138:
2128:
1891:
1806:
1789:
1616:
1079:
109:
1406:
172:
2433:
2428:
2161:
2156:
2133:
2035:
1847:
1645:
Norma P. Gerard, Roger L. Eddy, Jr., Thomas B . Shows, and Craig Gerard (1990)
1493:
1371:
1358:
Paige, Christopher J.; et al. (2006). "Tachykinins In The Immune System".
1321:
688:
451:
1180:
1032:
1015:
813:
2862:
2614:
2609:
2110:
2105:
2072:
759:
655:
622:
618:
609:
593:
543:
537:
2822:
2817:
2802:
2589:
2549:
2438:
2314:
2309:
2304:
2299:
2266:
2012:
1899:
1855:
1815:
1749:
1700:
1682:
1624:
1501:
1458:
1414:
1379:
1339:
1265:
1237:
1188:
1130:
1108:
1087:
1041:
997:
706:
1977:
1969:
1948:
1582:
1541:
2724:
2719:
2704:
2534:
2443:
2353:
2281:
2256:
2192:
2177:
2097:
2067:
2052:
763:
659:
638:
521:
512:
121:
1122:
570:
2832:
2778:
2773:
2729:
2689:
2684:
2669:
2664:
2654:
2594:
2559:
2554:
2544:
2245:
2209:
2199:
2182:
2148:
2120:
2077:
647:
555:
508:
439:
271:
250:
116:
2458:
948:
2847:
2827:
2768:
2763:
2634:
2383:
2368:
2214:
2204:
2187:
2044:
850:
534:
528:
450:
Except where otherwise noted, data are given for materials in their
2358:
2337:
2332:
2276:
810:
precursors encode synthesis of both Substance P and neurokinin A.
238:
2403:
2388:
2008:
755:
642:
552:
549:
307:
36:
1716:"An unidentified depressor substance in certain tissue extracts"
507:
Neurokinin A (formally known as substance K) is a member of the
97:
2324:
546:
540:
531:
191:
104:
1926:
1664:
1652:
Vol. 2fi.5, No. 33, Issue of November 25. pp. 20455–20462
27:
2237:
710:
702:
228:
1827:
Sun, J; Ramnath, RD; Tamizhselvi, R; Bhatia, M (Sep 2008).
1826:
53:
19:
1787:
1250:
766:
conformation is induced in the central core (Asp4-Met10).
654:
Neurokinin A has an inhibitory effect on the formation of
35:
of the tachykinin peptide Neurokinin A in the presence of
2463:
1430:
592:
into the epidermis, directly influence the activity of
786:
gene gives rise to four different peptide precursors (
516:
inflammatory responses. It is produced from the same
1955:
1431:
Kraan, J.; Vink-Klooster, H.; Postma, D. S. (2001).
1209:
953:
280:
2508:
1519:
1602:
2860:
319:
1479:
1065:
214:
2454:Pituitary adenylate cyclase-activating peptide
1713:
1647:The Human Neurokinin A (Substance K) Receptor.
939:
937:
935:
698:Tachykinins selectively bind and activate the
2494:
2374:Cocaine- and amphetamine-regulated transcript
1993:
1310:CNS & Neurological Disorders Drug Targets
954:Chandrashekar IR, Cowsik SM (December 2003).
896:gene and thus substance P and neurokinin A.
2007:
1392:
932:
2501:
2487:
2000:
1986:
1555:Nakanishi, Shigetada; et al. (1990).
258:
26:
1877:
1805:
1739:
1690:
1572:
1554:
1448:
1329:
1227:
1031:
1013:
987:
339:
1303:
869:
812:
687:
674:
569:
1714:v. Euler, U. S.; Gaddum, J. H. (1931).
297:
2861:
1783:
1781:
1779:
1765:
1763:
1761:
1759:
1660:
1658:
1598:
1596:
1594:
1592:
1522:Am J Physiol Regul Integr Comp Physiol
1515:
1513:
1511:
1304:Maudsley, Stuart; et al. (2010).
1299:
1297:
1295:
1166:
877:
734:genito-urinary and respiratory tract.
565:
2482:
1981:
1426:
1424:
1357:
1293:
1291:
1289:
1287:
1285:
1283:
1281:
1279:
1277:
1275:
1061:
1059:
665:
651:chemoattractor is currently unclear.
366:Key: HEAUFJZALFKPBA-JPQUDPSNSA-N
1919:
1353:
1351:
1349:
1216:Journal of Investigative Dermatology
1162:
1160:
1158:
1156:
1154:
1152:
1150:
1148:
1009:
1007:
1776:
1756:
1707:
1655:
1650:The Journal of Biological Chemistry
1639:
1589:
1508:
1473:
1437:Clinical & Experimental Allergy
1386:
769:
583:hypothalamic–pituitary–adrenal axis
376:Key: HEAUFJZALFKPBA-JPQUDPSNBV
310:
13:
1941:10.1111/j.1474-8673.1993.tb00396.x
1574:10.1111/j.1432-1033.1990.tb19396.x
1548:
1421:
1272:
1203:
1056:
899:
562:with amidation at the C-terminus.
14:
2885:
1929:Journal of Autonomic Pharmacology
1907:
1346:
1244:
1145:
1004:
599:
1880:European Journal of Pharmacology
1561:European Journal of Biochemistry
1534:10.1152/ajpregu.1998.275.6.R1803
1450:10.1046/j.1365-2222.2001.00975.x
1229:10.1046/j.0022-202x.2001.01498.x
716:
632:
458:
190:
2364:Calcitonin gene-related peptide
835:
823:
606:corticotropin-releasing hormone
502:
454:(at 25 °C , 100 kPa).
1732:10.1113/jphysiol.1931.sp002763
1102:
725:
1:
1014:Nakanishi, Shigetada (2006).
980:10.1016/S0006-3495(03)74814-0
926:
2379:Delta-sleep-inducing peptide
1892:10.1016/j.ejphar.2011.09.035
1807:10.1183/09031936.03.00101902
1794:European Respiratory Journal
1617:10.1016/j.neulet.2011.07.057
1080:10.1016/j.neulet.2005.06.011
745:
20:TAC1 tachykinin, precursor 1
7:
2869:Genes on human chromosome 7
1407:10.1056/nejm200010053431407
886:
700:G-protein coupled receptors
683:
10:
2890:
1848:10.1152/ajpcell.00042.2008
1494:10.2174/138945006778019291
1372:10.2174/138945006778019363
1322:10.2174/187152710793361504
1169:Behavioural Brain Research
737:
2787:
2738:
2519:
2399:Gastrin-releasing peptide
2346:
2323:
2292:
2236:
2227:
2170:
2147:
2119:
2096:
2043:
2034:
2019:
1836:Am J Physiol Cell Physiol
1181:10.1016/j.bbr.2010.04.044
1033:10.1080/15216540600746385
857:
840:
520:gene as the neuropeptide
448:
405:
385:
350:
198:
189:
168:
158:
153:
149:
132:
127:
115:
103:
91:
79:
67:
59:
49:
44:
25:
18:
1111:Pharmacological Reviews
829:pre-protachykinin-1 -/-
2449:Pancreatic polypeptide
1683:10.1038/sj.bjp.0704217
817:
695:
574:
2680:Nolpitantium besilate
921:Journal of Immunology
870:Psychiatric disorders
849:Patients with Midgut
816:
752:Phe-X-Gly-Leu-Met-NH2
691:
675:Cardiovascular system
573:
444:1133.32
2394:Galanin-like peptide
1605:Neuroscience Letters
1482:Current Drug Targets
1360:Current Drug Targets
1254:J Pharmacol Exp Ther
1068:Neuroscience Letters
2510:Neurokinin receptor
1771:Endocrine Abstracts
1123:10.1124/pr.54.2.285
972:2003BpJ....85.4002C
894:Pre-protachykinin-1
878:Affective disorders
784:pre-protachykinin-1
780:pre-protachykinin-2
776:pre-protachykinin-1
590:dorsal root ganglia
566:Mechanism of action
186:
1528:(6): R1803–R1811.
818:
696:
666:Respiratory system
575:
518:preprotachykinin A
481:Infobox references
184:
33:Solution structure
2856:
2855:
2476:
2475:
2472:
2471:
2223:
2222:
1401:(14): 1020–1034.
489:Chemical compound
487:
486:
240:Interactive image
182:
181:
178:
177:
2881:
2503:
2496:
2489:
2480:
2479:
2234:
2233:
2041:
2040:
2002:
1995:
1988:
1979:
1978:
1973:
1952:
1903:
1886:(2/3): 448–457.
1874:
1872:
1866:. Archived from
1833:
1820:
1819:
1809:
1785:
1774:
1767:
1754:
1753:
1743:
1711:
1705:
1704:
1694:
1662:
1653:
1643:
1637:
1636:
1600:
1587:
1586:
1576:
1552:
1546:
1545:
1517:
1506:
1505:
1488:(8): 1031–1042.
1477:
1471:
1470:
1452:
1428:
1419:
1418:
1390:
1384:
1383:
1366:(8): 1011–1020.
1355:
1344:
1343:
1333:
1301:
1270:
1269:
1248:
1242:
1241:
1231:
1222:(5): 1075–1082.
1207:
1201:
1200:
1164:
1143:
1142:
1106:
1100:
1099:
1063:
1054:
1053:
1035:
1026:(5/6): 349–357.
1011:
1002:
1001:
991:
951:
941:
770:Genetic overview
471:
465:
462:
461:
413:Chemical formula
343:
323:
312:
301:
284:
262:
242:
218:
194:
187:
183:
151:
150:
30:
16:
15:
2889:
2888:
2884:
2883:
2882:
2880:
2879:
2878:
2859:
2858:
2857:
2852:
2792:
2783:
2743:
2734:
2524:
2515:
2507:
2477:
2468:
2424:Neuropeptide VF
2419:Neuropeptide SF
2414:Neuropeptide FF
2409:Neuropeptide AF
2342:
2319:
2288:
2229:
2219:
2166:
2143:
2115:
2092:
2061:
2036:Opioid peptides
2030:
2015:
2006:
1976:
1922:
1920:Further reading
1910:
1870:
1831:
1823:
1786:
1777:
1768:
1757:
1712:
1708:
1663:
1656:
1644:
1640:
1601:
1590:
1553:
1549:
1518:
1509:
1478:
1474:
1429:
1422:
1391:
1387:
1356:
1347:
1302:
1273:
1249:
1245:
1208:
1204:
1165:
1146:
1107:
1103:
1064:
1057:
1012:
1005:
943:
942:
933:
929:
902:
900:Further reading
889:
880:
872:
860:
843:
838:
826:
772:
748:
740:
728:
719:
686:
677:
668:
635:
610:prefrontal lobe
602:
568:
505:
490:
483:
478:
477:
476: ?)
467:
463:
459:
455:
433:
429:
425:
421:
415:
401:
398:
393:
392:
381:
378:
377:
374:
368:
367:
364:
358:
357:
346:
326:
313:
287:
274:
265:
245:
232:
221:
208:
40:
12:
11:
5:
2887:
2877:
2876:
2871:
2854:
2853:
2851:
2850:
2845:
2840:
2835:
2830:
2825:
2820:
2811:
2810:
2805:
2796:
2794:
2790:
2785:
2784:
2782:
2781:
2776:
2771:
2766:
2757:
2756:
2747:
2745:
2741:
2736:
2735:
2733:
2732:
2727:
2722:
2717:
2712:
2707:
2702:
2697:
2692:
2687:
2682:
2677:
2672:
2667:
2662:
2657:
2652:
2647:
2642:
2637:
2632:
2627:
2622:
2617:
2612:
2607:
2602:
2597:
2592:
2587:
2582:
2577:
2572:
2567:
2562:
2557:
2552:
2547:
2538:
2537:
2528:
2526:
2522:
2517:
2516:
2506:
2505:
2498:
2491:
2483:
2474:
2473:
2470:
2469:
2467:
2466:
2461:
2456:
2451:
2446:
2441:
2436:
2434:Neuropeptide Y
2431:
2429:Neuropeptide S
2426:
2421:
2416:
2411:
2406:
2401:
2396:
2391:
2386:
2381:
2376:
2371:
2366:
2361:
2356:
2350:
2348:
2344:
2343:
2341:
2340:
2335:
2329:
2327:
2321:
2320:
2318:
2317:
2312:
2307:
2302:
2296:
2294:
2290:
2289:
2287:
2286:
2285:
2284:
2279:
2271:
2270:
2269:
2264:
2259:
2248:
2242:
2240:
2231:
2225:
2224:
2221:
2220:
2218:
2217:
2212:
2207:
2202:
2197:
2196:
2195:
2185:
2180:
2174:
2172:
2168:
2167:
2165:
2164:
2162:Leu-enkephalin
2159:
2157:Met-enkephalin
2153:
2151:
2145:
2144:
2142:
2141:
2136:
2131:
2125:
2123:
2117:
2116:
2114:
2113:
2108:
2102:
2100:
2094:
2093:
2091:
2090:
2088:β-Neoendorphin
2085:
2083:α-Neoendorphin
2080:
2075:
2070:
2065:
2064:
2063:
2059:
2049:
2047:
2038:
2032:
2031:
2023:
2021:
2017:
2016:
2005:
2004:
1997:
1990:
1982:
1975:
1974:
1953:
1923:
1921:
1918:
1917:
1916:
1909:
1908:External links
1906:
1905:
1904:
1875:
1873:on 2019-02-28.
1842:(3): C679–91.
1822:
1821:
1775:
1773:(2006) 11 OC23
1755:
1706:
1677:(1): 215–223.
1671:Br J Pharmacol
1654:
1638:
1588:
1567:(3): 751–757.
1547:
1507:
1472:
1443:(2): 274–278.
1420:
1385:
1345:
1316:(5): 627–635.
1271:
1243:
1202:
1175:(1): 103–108.
1144:
1117:(2): 285–322.
1101:
1074:(3): 194–198.
1055:
1003:
966:(6): 4002–11.
930:
928:
925:
924:
923:
918:
916:Science Direct
913:
908:
901:
898:
888:
885:
879:
876:
871:
868:
859:
856:
842:
839:
837:
834:
825:
822:
771:
768:
747:
744:
739:
736:
727:
724:
718:
715:
685:
682:
676:
673:
667:
664:
634:
631:
601:
600:Nervous system
598:
567:
564:
560:
559:
504:
501:
488:
485:
484:
479:
457:
456:
452:standard state
449:
446:
445:
442:
436:
435:
431:
427:
423:
419:
416:
411:
408:
407:
403:
402:
400:
399:
396:
388:
387:
386:
383:
382:
380:
379:
375:
372:
371:
369:
365:
362:
361:
353:
352:
351:
348:
347:
345:
344:
336:
334:
328:
327:
325:
324:
316:
314:
306:
303:
302:
295:
289:
288:
286:
285:
277:
275:
270:
267:
266:
264:
263:
255:
253:
247:
246:
244:
243:
235:
233:
226:
223:
222:
220:
219:
211:
209:
204:
201:
200:
196:
195:
180:
179:
176:
175:
170:
166:
165:
160:
156:
155:
147:
146:
136:
130:
129:
125:
124:
119:
113:
112:
107:
101:
100:
95:
89:
88:
83:
77:
76:
71:
65:
64:
61:
57:
56:
51:
47:
46:
42:
41:
31:
23:
22:
9:
6:
4:
3:
2:
2886:
2875:
2872:
2870:
2867:
2866:
2864:
2849:
2846:
2844:
2841:
2839:
2836:
2834:
2831:
2829:
2826:
2824:
2821:
2819:
2816:
2813:
2812:
2809:
2806:
2804:
2801:
2798:
2797:
2795:
2793:
2786:
2780:
2777:
2775:
2772:
2770:
2767:
2765:
2762:
2759:
2758:
2755:
2752:
2749:
2748:
2746:
2744:
2737:
2731:
2728:
2726:
2723:
2721:
2718:
2716:
2713:
2711:
2708:
2706:
2703:
2701:
2698:
2696:
2693:
2691:
2688:
2686:
2683:
2681:
2678:
2676:
2673:
2671:
2668:
2666:
2663:
2661:
2658:
2656:
2653:
2651:
2648:
2646:
2643:
2641:
2638:
2636:
2633:
2631:
2628:
2626:
2623:
2621:
2618:
2616:
2615:Fosnetupitant
2613:
2611:
2610:Fosaprepitant
2608:
2606:
2603:
2601:
2598:
2596:
2593:
2591:
2588:
2586:
2583:
2581:
2578:
2576:
2573:
2571:
2568:
2566:
2563:
2561:
2558:
2556:
2553:
2551:
2548:
2546:
2543:
2540:
2539:
2536:
2533:
2530:
2529:
2527:
2525:
2518:
2514:
2511:
2504:
2499:
2497:
2492:
2490:
2485:
2484:
2481:
2465:
2462:
2460:
2457:
2455:
2452:
2450:
2447:
2445:
2442:
2440:
2437:
2435:
2432:
2430:
2427:
2425:
2422:
2420:
2417:
2415:
2412:
2410:
2407:
2405:
2402:
2400:
2397:
2395:
2392:
2390:
2387:
2385:
2382:
2380:
2377:
2375:
2372:
2370:
2367:
2365:
2362:
2360:
2357:
2355:
2352:
2351:
2349:
2345:
2339:
2336:
2334:
2331:
2330:
2328:
2326:
2322:
2316:
2313:
2311:
2308:
2306:
2303:
2301:
2298:
2297:
2295:
2291:
2283:
2280:
2278:
2275:
2274:
2272:
2268:
2265:
2263:
2260:
2258:
2255:
2254:
2252:
2249:
2247:
2244:
2243:
2241:
2239:
2235:
2232:
2230:neuropeptides
2226:
2216:
2213:
2211:
2208:
2206:
2203:
2201:
2198:
2194:
2191:
2190:
2189:
2186:
2184:
2181:
2179:
2176:
2175:
2173:
2169:
2163:
2160:
2158:
2155:
2154:
2152:
2150:
2146:
2140:
2137:
2135:
2132:
2130:
2127:
2126:
2124:
2122:
2118:
2112:
2111:Endomorphin-2
2109:
2107:
2106:Endomorphin-1
2104:
2103:
2101:
2099:
2095:
2089:
2086:
2084:
2081:
2079:
2076:
2074:
2073:Big dynorphin
2071:
2069:
2066:
2062:
2056:
2055:
2054:
2051:
2050:
2048:
2046:
2042:
2039:
2037:
2033:
2029:
2028:
2022:
2018:
2014:
2013:neuropeptides
2010:
2003:
1998:
1996:
1991:
1989:
1984:
1983:
1980:
1971:
1967:
1964:(4): 551–99.
1963:
1959:
1958:Pharmacol Rev
1954:
1950:
1946:
1942:
1938:
1934:
1930:
1925:
1924:
1915:
1912:
1911:
1901:
1897:
1893:
1889:
1885:
1881:
1876:
1869:
1865:
1861:
1857:
1853:
1849:
1845:
1841:
1837:
1830:
1825:
1824:
1817:
1813:
1808:
1803:
1799:
1795:
1791:
1784:
1782:
1780:
1772:
1766:
1764:
1762:
1760:
1751:
1747:
1742:
1737:
1733:
1729:
1725:
1721:
1717:
1710:
1702:
1698:
1693:
1688:
1684:
1680:
1676:
1672:
1668:
1661:
1659:
1651:
1648:
1642:
1634:
1630:
1626:
1622:
1618:
1614:
1610:
1606:
1599:
1597:
1595:
1593:
1584:
1580:
1575:
1570:
1566:
1562:
1558:
1551:
1543:
1539:
1535:
1531:
1527:
1523:
1516:
1514:
1512:
1503:
1499:
1495:
1491:
1487:
1483:
1476:
1468:
1464:
1460:
1456:
1451:
1446:
1442:
1438:
1434:
1427:
1425:
1416:
1412:
1408:
1404:
1400:
1396:
1389:
1381:
1377:
1373:
1369:
1365:
1361:
1354:
1352:
1350:
1341:
1337:
1332:
1327:
1323:
1319:
1315:
1311:
1307:
1300:
1298:
1296:
1294:
1292:
1290:
1288:
1286:
1284:
1282:
1280:
1278:
1276:
1267:
1263:
1260:(2): 449–58.
1259:
1255:
1247:
1239:
1235:
1230:
1225:
1221:
1217:
1213:
1206:
1198:
1194:
1190:
1186:
1182:
1178:
1174:
1170:
1163:
1161:
1159:
1157:
1155:
1153:
1151:
1149:
1140:
1136:
1132:
1128:
1124:
1120:
1116:
1112:
1105:
1097:
1093:
1089:
1085:
1081:
1077:
1073:
1069:
1062:
1060:
1051:
1047:
1043:
1039:
1034:
1029:
1025:
1021:
1017:
1010:
1008:
999:
995:
990:
985:
981:
977:
973:
969:
965:
961:
957:
950:
946:
940:
938:
936:
931:
922:
919:
917:
914:
912:
909:
907:
904:
903:
897:
895:
884:
875:
867:
863:
855:
852:
847:
833:
830:
821:
815:
811:
809:
805:
801:
797:
793:
789:
785:
781:
777:
767:
765:
764:alpha helical
761:
760:cell membrane
757:
753:
743:
735:
732:
723:
717:NK-2 receptor
714:
712:
708:
704:
701:
694:
690:
681:
672:
663:
661:
657:
656:myeloid cells
652:
649:
644:
640:
633:Immune system
630:
626:
624:
623:interleukin-6
620:
619:interleukin-1
614:
611:
607:
597:
595:
594:keratinocytes
591:
587:
584:
579:
572:
563:
557:
554:
551:
548:
545:
542:
539:
536:
533:
530:
527:
526:
525:
523:
519:
514:
510:
500:
498:
494:
482:
475:
470:
453:
447:
443:
441:
438:
437:
417:
414:
410:
409:
404:
395:
394:
391:
384:
370:
360:
359:
356:
349:
342:
338:
337:
335:
333:
330:
329:
322:
318:
317:
315:
309:
305:
304:
300:
296:
294:
291:
290:
283:
279:
278:
276:
273:
269:
268:
261:
257:
256:
254:
252:
249:
248:
241:
237:
236:
234:
230:
225:
224:
217:
213:
212:
210:
207:
203:
202:
197:
193:
188:
185:Neurokinin A
174:
171:
167:
164:
161:
157:
152:
148:
145:
144:
140:
137:
135:
131:
126:
123:
120:
118:
114:
111:
108:
106:
102:
99:
96:
94:
90:
87:
84:
82:
78:
75:
72:
70:
66:
62:
58:
55:
52:
48:
43:
38:
34:
29:
24:
21:
17:
2823:Fezolinetant
2818:Elinzanetant
2815:Antagonists:
2814:
2803:Neurokinin B
2799:
2761:Antagonists:
2760:
2754:Neurokinin A
2753:
2750:
2590:Elinzanetant
2550:Befetupitant
2542:Antagonists:
2541:
2531:
2439:Neurophysins
2267:Neurokinin B
2262:Neurokinin A
2261:
2098:Endomorphins
2024:
1961:
1957:
1935:(1): 23–93.
1932:
1928:
1883:
1879:
1868:the original
1839:
1835:
1800:(1): 76–81.
1797:
1793:
1770:
1726:(1): 74–87.
1723:
1719:
1709:
1674:
1670:
1649:
1641:
1611:(1): 23–26.
1608:
1604:
1564:
1560:
1550:
1525:
1521:
1485:
1481:
1475:
1440:
1436:
1398:
1395:N Engl J Med
1394:
1388:
1363:
1359:
1313:
1309:
1257:
1253:
1246:
1219:
1215:
1205:
1172:
1168:
1114:
1110:
1104:
1071:
1067:
1023:
1019:
963:
959:
893:
890:
881:
873:
864:
861:
848:
844:
836:Applications
828:
827:
824:Mouse models
819:
807:
803:
799:
795:
791:
787:
783:
779:
775:
773:
762:system), an
751:
749:
741:
730:
729:
720:
709:(NK2R), and
697:
692:
678:
669:
653:
636:
627:
615:
603:
580:
576:
561:
558:(HKTDSFVGLM)
506:
503:Introduction
496:
493:Neurokinin A
492:
491:
299:Neurokinin+A
199:Identifiers
141:
60:Alt. symbols
2725:Vestipitant
2720:Tradipitant
2715:Telmapitant
2705:Serlopitant
2700:SDZ NKT 343
2535:Substance P
2444:Neurotensin
2354:Angiotensin
2293:Neuromedins
2282:Physalaemin
2257:Substance P
2251:Tachykinins
2246:Bradykinins
2193:Hemorphin-4
2178:Adrenorphin
2149:Enkephalins
2139:γ-Endorphin
2134:β-Endorphin
2129:α-Endorphin
2068:Dynorphin B
2058:Dynorphin A
2053:Dynorphin A
726:Antagonists
660:substance P
639:nociceptors
522:substance P
513:nociceptive
406:Properties
163:Swiss-model
45:Identifiers
2863:Categories
2843:SB-222,200
2838:SB-218,795
2833:Pavinetant
2779:Saredutant
2774:Nepadutant
2730:Vofopitant
2690:Rolapitant
2685:Orvepitant
2670:Netupitant
2665:Maropitant
2655:Lanepitant
2600:Figopitant
2595:Ezlopitant
2560:Casopitant
2555:Burapitant
2545:Aprepitant
2513:modulators
2273:amphibian
2210:Spinorphin
2200:Nociceptin
2183:Amidorphin
2121:Endorphins
2078:Leumorphin
2045:Dynorphins
1720:J. Physiol
1020:IUBMB Life
960:Biophys. J
927:References
804:alpha tac1
648:leukocytes
509:tachykinin
440:Molar mass
341:94168F9W1D
272:IUPHAR/BPS
251:ChemSpider
227:3D model (
216:86933-74-6
206:CAS Number
159:Structures
154:Search for
128:Other data
63:TAC2, NKNA
2848:Talnetant
2828:Osanetant
2800:Agonists:
2769:Ibodutant
2764:GR-159897
2751:Agonists:
2660:LY-306740
2650:L-758,298
2645:L-743,310
2640:L-741,671
2635:L-733,060
2625:GW-597599
2620:GR-203040
2580:CP-122721
2532:Agonists:
2384:FMRFamide
2369:Carnosine
2253:: mammal
2215:Valorphin
2205:Opiorphin
2188:Hemorphin
952:;
851:Carcinoid
808:beta tac1
798:tac1 und
758:(a model
746:Structure
731:MEN 11420
110:NM_013998
69:NCBI gene
2874:Peptides
2808:Senktide
2695:RP-67580
2585:Dapitant
2575:CP-99994
2570:CP-96345
2359:Bombesin
2277:Kassinin
2027:hormones
2020:Hormones
2009:Peptides
1900:21958872
1864:23891934
1856:18596216
1816:14738235
1750:16994201
1701:11522614
1633:19457550
1625:21855604
1502:16918331
1467:33502100
1459:11251629
1415:11018170
1380:16918329
1340:20632965
1266:11602654
1238:11710915
1197:32597979
1189:20438764
1139:85570180
1131:12037144
1096:22944646
1088:16005149
1042:16754330
998:14645089
887:Epilepsy
756:micelles
705:(NK1R),
684:Receptor
434:S
173:InterPro
37:micelles
2675:NKP-608
2630:HSP-117
2565:CI-1021
2459:RVD-Hpα
2404:Ghrelin
2389:Galanin
2325:Orexins
1970:7534932
1949:8382703
1914:Journal
1741:1403098
1692:1572917
1583:1701145
1542:9843869
1331:2967650
1050:9831413
989:1303701
968:Bibcode
911:AJPLUNG
738:History
643:T-cells
474:what is
472: (
308:PubChem
260:4470818
169:Domains
143:q21-q22
117:UniProt
2710:T-2328
2605:FK-888
2238:Kinins
2171:Others
1968:
1947:
1898:
1862:
1854:
1814:
1748:
1738:
1699:
1689:
1631:
1623:
1581:
1540:
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1338:
1328:
1264:
1236:
1195:
1187:
1137:
1129:
1094:
1086:
1048:
1040:
996:
986:
858:Asthma
841:Cancer
794:tac1,
790:tac1,
469:verify
466:
390:SMILES
139:Chr. 7
122:P20366
105:RefSeq
98:162320
50:Symbol
2347:Other
2228:Other
1871:(PDF)
1860:S2CID
1832:(PDF)
1629:S2CID
1463:S2CID
1193:S2CID
1135:S2CID
1092:S2CID
1046:S2CID
800:gamma
796:delta
788:alpha
711:TACR3
707:TACR2
703:TACR1
355:InChI
321:55582
229:JSmol
134:Locus
86:11517
2025:see
1966:PMID
1945:PMID
1896:PMID
1852:PMID
1812:PMID
1746:PMID
1697:PMID
1621:PMID
1579:PMID
1538:PMID
1498:PMID
1455:PMID
1411:PMID
1376:PMID
1336:PMID
1262:PMID
1234:PMID
1185:PMID
1127:PMID
1084:PMID
1038:PMID
994:PMID
949:1N6T
906:NCBI
806:and
792:beta
778:and
774:The
621:and
332:UNII
293:MeSH
282:2089
93:OMIM
81:HGNC
74:6863
54:TAC1
2464:VGF
2060:1–8
1937:doi
1888:doi
1884:670
1844:doi
1840:295
1802:doi
1736:PMC
1728:doi
1687:PMC
1679:doi
1675:134
1613:doi
1609:503
1569:doi
1565:193
1530:doi
1526:275
1490:doi
1445:doi
1403:doi
1399:343
1368:doi
1326:PMC
1318:doi
1258:299
1224:doi
1220:117
1177:doi
1173:213
1119:doi
1076:doi
1072:386
1028:doi
984:PMC
976:doi
945:PDB
556:Met
553:Leu
550:Gly
547:Val
544:Phe
541:Ser
538:Asp
535:Thr
532:Lys
529:His
497:NKA
311:CID
2865::
2789:NK
2740:NK
2521:NK
2011::
1962:46
1960:.
1943:.
1933:13
1931:.
1894:.
1882:.
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1796:.
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1113:.
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1024:58
1022:.
1018:.
1006:^
992:.
982:.
974:.
964:85
962:.
958:.
947::
934:^
432:14
428:14
424:80
420:50
2791:3
2742:2
2523:1
2502:e
2495:t
2488:v
2338:B
2333:A
2315:U
2310:S
2305:N
2300:B
2001:e
1994:t
1987:v
1972:.
1951:.
1939::
1902:.
1890::
1846::
1818:.
1804::
1752:.
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1492::
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1342:.
1320::
1314:9
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1199:.
1179::
1141:.
1121::
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1052:.
1030::
1000:.
978::
970::
495:(
464:N
430:O
426:N
422:H
418:C
231:)
39:.
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