Tachykinin NK1 receptor

The striatum, the nucleus accumbens, the hippocampus, the lateral nucleus of the hypothalamus, the habenula, the interpeduncular nucleus, the nucleus of the tractus soli-tarius, the raphe nuclei and the medulla oblongata are rich in tachykinin NK1 receptors (Otsuka and Yoshioka, 1993). The predominant expression of N receptors within the spinal dorsal horn is consistent with the assumption that SP and NKA are important messengers here (Bleazard et al., 1994). The distribution of NKi receptors in the peripheral nervous system and in the gut are discussed elsewhere (McLean, 1996 Quartara and Maggi, 1997, 1998). 

Beattie, D. T., Connor, H. E., Hagan, R. M. Recent developments in tachykinin NK1 receptor antagonists prospects for the treatment of migraine headache, Can. J. Physiol. Pharmacol. 1995a, 73, 871-877. 

Ma, Q.-P. and Woolf, C. J. Tachykinin NK1 receptor antagonist RP67580 attenuates progressive... 

Maggi, C. A. and Schwartz, T. W. The dual nature of the tachykinin NK1 receptor, Trends Pharmacol. 

Quartara, L. and Maggi, C.A. The tachykinin NK1 receptor Part II. Distribution and pathophysiological roles, Neuropeptides 1998, 32, 1-49. 

Holst, B., Hastrup, H., Raffetseder, U., Martini, L., and Schwartz, T. W. (2001). Two active molecular phenotypes of the tachykinin NK1 receptor revealed by G-protein fusions and mutagenesis. / Biol. Chem. 276, 19793-19799. 

Non-peptidic tachykinine antagonists were converted to photoprobe ligands by Ward. First, a piperidine derivative, CP-99,994 (Glaxo) was appended with a diazirine photophore (6, Fig. 7) to study SP (NK1) receptors [74]. A similar modification on a neurokinin A antagonist, SR 48968 (Sanofi) produced a photoligand (5, Fig. 7) in order to investigate NK2 receptor proteins [75]. 

Bleazard, L., Hill, R. G., Morris, R. The correlation between the distribution of the NK1 receptor and the actions of tachykinin agonists in the dorsal horn of the rat indicates that substance P does not have a functional role on substantia gelatinosa (lamina II) neurons, J. Neurosci. 1994, 14, 7655-7664. 

O Shaughnessy, C. T. and Connor, H. E.. Investigation of the role of tachykinin Nk1, NK2 receptors and CGRP receptors in neurogenic plasma protein extravasation in dura mater, Eur. J. Pharmacol. 1994, 263, 193-198. 

Akasu T, Ishimatsu M, Yamada K. 1996. Tachykinins cause inward current through NK1 receptors in bullfrog sensory neurons. Brain Res 713 160-167. 

Substance P acts via tachykinin NK1 and NK2 receptors, these being coupled via G proteins resulting in PLC activation, IP3 generation and cytosolic Ca2+ elevation. 

In the fields of allergy and respiration, examples include 2-oxo-3-aminoazepine derivatives which act as dual neurokinin (tachykinin) NK1/NK2 receptor probes for development of options for treatment of asthsma and other airway diseases <07BMCL890> and benzo[l, 5]diazepine derivatives as new non-steroidal inhibitors of 17-P-hydroxysteroid dehydrogenase, an enzyme associated with hormone-dependent and neuronal diseases <07JEIMC29>. 

Because of specific cluster structure determined by the internal activation (neuron) function originally realized in the Kohonen-based SOMs it is very difficult to obtain a fully scalable and, at the same time, adequate map with the preservation of all the distances observed among all input samples. Fortunately, using the constructed map it is quite possible to set the zoom into the GPCR area. Thus, compounds acting specifically on different GPCR subclasses including a/ p-adrenoceptors, dopamine D1-D4 receptors, tachykinin NK1/NK2, serotonin and chemokine receptors can also be successfully separated within the same map (Fig. 3a-i). 

Walpole, C., Ko, S. Y., Brown, M., Beattie, D., Campbell, E., Dickenson, F., Ewan, S., Hughes, G. A., Lemaire, M., Lerpiniere, J., Patel, S., Urban, L. 2-Nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide (SDZ NKT 343), a potent human NK1 tachykinin receptor antagonist with good oral analgesic activity in chronic pain models, J. Med. Chem. 1998b, 41, 3159-3173. 

Tachykinins are a group of biologically active neuropeptide hormones implicated in a variety of biological processes such as pain transmission, inflammation, vasodialation, and secretion (Burcher et al., 1995). The effect of tachykinins is modulated via the specific G-protein coupled receptors like NK1 and NK2. Thus non-peptide NK-receptors antagonists are potentially useful in the treatment of variety of chorinic diseases including asthma, bron-chospasm, arthritis, and migraine (Veronesi et al., 1999 Yuan et al., 1998). The... 

Wijkhuisen A, Sagot MA, Frobert Y, Creminon C, Grassi J, et al. 1999. Identification in the NK1 tachykinin receptor of... 

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