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Tachykinins

A family of closely related short amidated neuropeptides identified initially by their activities as neurotransmitters. Many of these compounds were identified initially in mollusks and amphibians (frog Physalaemin) and were later found also in vertebrates and invertebrates (Drosophila melanogaster, locusts). These peptides play an important role as neuromodulators and are involved in such different processes as stress regulation (see also: Neuroimmune network), pain, and control of vascular tonus.

The tachykinin family includes SP (substance P = NK1, Neurokinin-1), Neurokinin A (= NK2, Neurokinin-2, Substance K, abbr. SK; known also as neuropeptide K (abbr. NPK) = Neurokinin-alpha, Neuromedin L), Neurokinin B (= NK3, Neurokinin-3, Neurokinin-beta, Neuromedin K), Hemokinin-1, and Endokinins.

Of the two human genes one (NKNA, chromosome 7q21-q22) encodes substance P and neurokinin A. The new designation for this gene is Tac1 [Tachykinin-1] (formerly Tachykinin-2) The other gene (NKNB, chromosome 12q13-q21) encodes a precursor containing neurokinin B only. The new designation for Neurokinin B or Neuromedin K is Tachykinin-3.

Some tachykinins arise by differential splicing of the RNA transcript of the prepro-tachykinin (PTT) gene and by differential proteolytic processing of the preproprotein (Krause et al, 1987). Three forms of message (alpha, beta, and gamma) arise by alternative splicing events with the beta and gamma forms of prepro-tachykinins encoding both substance P and neurokinin A, and the alpha form containing only the substance P sequence. The expression of the PTT gene is subject to regulation by NGF. Neuropeptide-gamma is an N-terminal extended form of neurokinin A (gamma-prepro-tachykinin 72-92).


tachykin
Amino acid sequences of some tachykinins.

This sequence comparison shows the conserved aminoterminal sequences. All factors with the exception of Neurokinin B (NKB) are encoded by the PPTI gene (Prepro-Tachykinin-I). NKB is encoded by the PPTII gene.


The three known tachykinin receptors belong to the group of receptors coupled to G-proteins. These receptors are characterized by a highly conserved transmembrane domain which passes seven times through the membrane. The receptors (neurokinin receptors) are called NK1 (substance P-specific), NK2 (Neurokinin A-specific; binds neuropeptide gamma) and NK3 (Neurokinin B-specific). These receptors also bind Bombesin and Bombesin-like peptides such as GRP (gastrin releasing hormone).

Apart from the classical role as neurotransmitters tachykinins also show cytokine-like activities although they are not seen or classified as cytokines due to their small sizes (see also: regulatory peptide factors). Tachykinins stimulate the proliferation of T-cells, enhance the mitogen induced release of cytokines such as IFN-gamma, TNF-alpha, IL1 and IL6 by granulocytes and macrophages, enhance the secretion of immunoglobulins, and also mediate chemotactic and phagocytic processes (see also: Chemotaxis).

Tachykinins cause cell activation of neutrophilic granulocytes, they induce the synthesis of adhesion molecules in endothelial cells, and they are involved in the regulation of non-infectious inflammatory processes. Neuromedin B and neuromedin C stimulate the growth of fibroblasts and smooth muscle cells. They are also mitogenic for small cell lung carcinomas and act as autocrine growth modulators. Neurokinin A and SP (substance P) inhibit chemotactic migration of neutrophils induced by IL8. Neurokinin A and neurokinin B and also substance P promote the synthesis of IL1.

For other entries pertaining to low molecular weight substances that are not classified as cytokines or growth factors but that possess activities of cytokines see also: regulatory peptide factors.


Copyright 2012 by H IBELGAUFTS. All rights reserved.
ENTRY LAST MODIFIED: January 2002



 

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