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Tachykinins pp 25–61Cite as

The Tachykinin Peptide Family, with Particular Emphasis on Mammalian Tachykinins and Tachykinin Receptor Agonists

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 164))

Abstract

The tachykinins, substance P (SP), neurokinin A (NKA), neuropeptide γ (NPγ) and neuropeptide K (NPK) are encoded by the single copy preprotachykinin A (PPT-A) gene on chromosome 7. Four tachykinin precursors (α-, β-, γ- and δ-PPT-A) arise from this gene by an alternative RNA splicing mechanism. The preprotachykinin B gene on chromosome 12 encodes the precursor of neurokinin B (NKB). The preprotachykinin C gene on chromosome 17 encodes a protein that contains the sequence of hemokinin 1(HK-1) and two peptides with limited structural similarity to SP,termed endokinin C and endokinin D. The actions of the tachykinins are mediated through activation of the NK1, NK2 and NK3 receptors. However, NH2-terminal fragments of SP such as SP (1–7) exert behavioral and other effects when administered centrally that appear not to be mediated through direct interaction with these receptors. Analogs of SP such as [Sar9]SP sulfone, and peptidase-resistant agonists such as GR73632, show greater potency and selectivity than SP for the NK1 receptor. Septide {[pGlu6,Pro9SP(6–11)}, although a poor competitor for radiolabeled SP in ligand binding assays, is a potent and selective agonist in many functional assays that involve activation of NK1 receptors. Septide is believed to bind to a distinct ‘septide sensitive’ site on the NK1 receptor. Analogs such as [Lys5,MeLeu9,Nle10] NKA(4–10) and [βAla8]NKA(4–10) show higher affinity and selectivity than NKA for the NK2 receptor and [MePhe7]NKB and senktide {succinyl-[Asp6, MePhe8]SP(6-11)} are more selective than NKB for the NK3 receptor. NPK and NPγ are preferred agonists for the NK2 receptor. The NH2 terminal extension to the NKA sequence in these tachykinins has only minor effects on potency in vitro but the greater stability of these agonists in vivo results in a different spectrum of activities. The physiological role of HK-1 remains to be firmly established but the peptide has a pharmacological profile similar to that of SP. Endokinins C and D display only very weak tachykinin-like bioactivity. Orthologs of the mammalian tachykinins have been isolated from the tissues of nonmammalian vertebrates ranging from birds to lampreys and analysis of their amino acid sequences and properties gives insight into structure-activity relationships.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, 17666, Al-Ain, United Arab Emirates

    J. M. Conlon

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  1. J. M. Conlon
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  1. Department of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010, Graz, Austria

    Peter Holzer (Professor) (Professor)

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Conlon, J.M. (2004). The Tachykinin Peptide Family, with Particular Emphasis on Mammalian Tachykinins and Tachykinin Receptor Agonists. In: Holzer, P. (eds) Tachykinins. Handbook of Experimental Pharmacology, vol 164. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18891-6_2

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  • DOI: https://doi.org/10.1007/978-3-642-18891-6_2

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