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Overview of the Primary Structure, Tissue-Distribution, and Functions of Tachykinins and their Receptors

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Tachykinins (TKs) constitute the largest vertebrate brain/gut peptide family. Since discovery of Substance P as a structurally unidentified vasodilatory and contractile compound in 1931, continuous and tremendous advances have been made regarding molecular and functional characterization of TKs and their receptors, revealing diverse molecular species of TK peptides with a C-terminal consensus -Phe-X-Gly-Leu-Met-NH2, not ubiquitous but wide distribution and multiple biological activities of TKs and their receptors in central and peripheral tissues, elaborate and complicated ligand-recognition and multiple functional conformation of receptors, evolutionary aspects of brain/gut peptides, and the implication of TK peptides and receptors in many disorders of current keen interest. Indeed, the tachykinergic systems are now regarded as promising targets of novel clinical agents aimed at a variety of pathological symptoms and processes such as nociception, inflammation, neurodegeneration, and neuroprotection. In this review, we present an overview of basic knowledge and a buildup of recent advances in extensive fields of the 'tachykinin kingdom' including mammalian non-neuronal TKs, invertebrate salivary gland-specific TKs and TK-related brain/gut peptides (TKRPs). These findings shed new light on (1) the biological and biochemical significance of TKs, (2) evolutionary relationship of the structures and functions between mammalian and non-mammalian TK family peptides and receptors, and (3) the binding mode for the TK family peptides and their receptors and the resultant activation of the complexes that are essential for design and development of leading compounds.

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Keywords: Tachykinin; activity; conformation; receptor; signal transduction

Document Type: Research Article

Affiliations: Suntory Institute for Bioorganic Research, 1-1-1 Wakayamadai, Shimamoto, Mishima, Osaka 618-8503, Japan.

Publication date: 2006-08-01

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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