Tachykinin neurokinin

The oocyte system has also been utilized by Turcatti et al. to incorporate a fluorescent amino acid into the tachykinin neurokinin-2 receptor (NK2), al-... 

Substance P and the related tachykinins neurokinin A and neurokinin B are mainly found in neurons, particularly unmyelinated sensory somatic and visceral fibres, in enteric sensory neurons and in a number of pathways within the brain. The release of tachykinins from the peripheral ends of these neurons may play an important role in the neurogenic inflammatory responses to local injury and inflammation by promoting the release of histamine from mast cell degranulation, and the release of cytokines from invading white cells, as well as acting directly upon blood vessels to produce vasodilation and plasma extravasation. Neurogenic inflammation within... 

Hua, X.Y., Theodorsson-Noreim, E., Brodin, E. et al. (1985). Multiple tachykinins (neurokinin A, neuropeptide K and substance P) in capsaicin-sensitive sensory neurons in the guinea-pig. Regul. Pept. 13, 1-19. 

Tachykinins Neurokinins A and B Substance P Insulin Vasopressin Cholecystokinin Somatostatin Neurotensin Bombesin... 

A. Chollet, Probing the structure and function of the tachykinin neurokinin-2 receptor through biosynthetic incorporation of fluorescent amino acids at specific sites,/. Biol. Chem. 1996, 271, 19991-19998. 

As an example of a similar approach using in vivo SNAAR, Turcatti et aL" " incorporated a fluorescent amino acid, 3-N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl)-2,3-diaminopropionic acid (NBD-Dpr), at specific sites in the tachykinin neurokinin-2 receptor, a member of the large family of seven a-helix G-protein coupled receptors (GPCRs). The expression system, Xenopus oocytes, allowed for functional assays of the receptor. Structural information was obtained by measuring the intermolecular distance between the fluorescent amino acids placed at different sites and a fluorescently labeled heptapeptide antagonist using fluorescence resonance energy transfer (FRET). 

Xurcatti, G., Nemeth, K., Edgerton, M.D., Meseth, U., Talabot, F., Peitsch, M., Knowles, J., Vogel, H., and ChoUet, A., Probing the structure and function of the tachykinin neurokinin-2 receptor through biosynthetic incorporation of fluorescent amino acids at specific sites, /. Biol. Chem., 271, 33,19991,1996. 

The group of peptides known as tachykinins include substance P, substance K or neurokinin A, and neuromedin K, ie, neurokinin B, as well as a number of nonmammalian peptides. All members of this family contain the conserved carboxy-terrninal sequence Phe-X-Gly-Leu-Met-NH2, where X is an aromatic, ie, Phe or Tyr, or branched aliphatic, eg, Val or lie, amino acid. In general, this C-terminal sequence is cmcial for tachykinin activity (33) in fact, both the methionineamide and the C-terminal amide are cmcial for activity. The nature of the X residue in this sequence determines pharmacological identity (34,35) thus the substance P group contains an aromatic residue in this position, while the substance K group contains an aliphatic residue (33). 

C-fibre afferents from the aitways contain peptide tachykinin transmitters such as substance P (SP) and neurokinins A and B (NKA and NKB). Stimulation of these nerves can also cause local release of these mediators at their peripheral terminal, allowing them to enhance the activity of the RARs. SP, NKA and NKB act at the tachykinin receptors (NK4-NK3), and so understandably, antagonists for NK2 in particular appear promising in cough. 

The neuropeptides are peptides acting as neurotransmitters. Some form families such as the tachykinin family with substance P, neurokinin A and neurokinin B, which consist of 11 or 12 amino acids and possess the common carboxy-terminal sequence Phe-X-Gly-Leu-Met-CONH2. Substance P is a transmitter of primary afferent nociceptive neurones. The opioid peptide family is characterized by the C-terminal sequence Tyr-Gly-Gly-Phe-X. Its numerous members are transmitters in many brain neurones. Neuropeptide Y (NPY), with 36 amino acids, is a transmitter (with noradrenaline and ATP) of postganglionic sympathetic neurones. 

Substance P is a member of a group of polypeptides known as neurokinins or tachykinins. It is thought to be the primary neurotransmitter for the transfer of sensory information from the periphery to the spinal cord and brain. Substance P as well as neurokinin NKX receptors has been detected in vagal afferent neurons in the area postrema, nucleus tractus solitarius and dorsal motor nucleus of the vagus. Substance P has been shown to increase the firing rate of neurons in the area postrema and nucleus tractus solitarius and to produce retching when applied directly to these areas in animal studies. 

Tachykinin NH receptor TK N r Neurokinin-1 receptor, substance P receptor... 

Tachykinin NK2 receptor TK NK2r Neurokinin-2 receptor, neurokinin A receptor, substance K receptor, neurokinin-alpha receptor, Neuromedin L receptor... 

Tachykinin NK3 receptor TK NK3r Neurokinin-3 receptor, neurokinin B receptor, neurokinin-beta receptor, Neuromedin K receptor... 

The common C-terminal amino acid sequence required for exerting activity at tachykinin receptors is shown in bold endokinin C and D lack the C-terminal Met and are almost devoid of affinity at these receptors. In red, the sequence of neurokinin A of which neuropeptide-gamma and neuropeptide-kappa are elongated forms and neurokinin A (3-10) is a product of beta or gamma-TAC1 mRNAs or an NKA metabolite active at tachykinin receptors. In blue, the sequence of human HK-1 of which endokinin A and B are elongated forms. 

These are a family of peptides which include substance P, isolated in 1931 but only sequenced in 1971. This peptide has been extensively studied since it was the first major peptide to be extracted from brain but only now are useful antagonists becoming available. Two closely related peptides were then isolated from mammalian tissues and can be added to a number of other tachykinins, many of which are found in amphibians. The name tachykinins originated from the vasoactive effects of substance P but the nomenclature has been resolved into calling the three major mammalian peptides substance P, neurokinin A (NKA) and neurokinin B (NKB) with the corresponding receptors being numbered 1 to 3. The order of potencies at the three receptors as follows ... 

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]. 

Dopamine D2 antagonists, Tachykinin NK3 antagonists, Neurokinin NK3 antagonists, etc. 

Keywords Substance P Neurokinin 1 Tachykinin Anxiety Knockout model... 

Tachykinins are among the most abundant neuropeptides in the central nervous system. Limbic structures, which are important in the control of emotional behaviors, in particular contain tachykinins and neurokinin receptor sites in high density (Honkaniemi et al. 1992 Hurd et al. 1999 Ribeiro-da-... 

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