Tachykinins
Tachykinins are peptides that occur as neurotransmitters and tissue hormones in many animal organisms. They belong to the group of neuropeptides . The tachykinins include substance P , neurokinin A , neurokinin B , hemokinin 1 , endokinin A and endokinin B , among others . The tachykinins owe their name to their ability to cause rapid contraction of smooth muscles . In addition, tachykinins have effects on the nervous system , endocrine system and immune system . They convey their physiological effects by activating tachykinin receptors .
Occurrence
Tachykinins are widespread in the realm of multicellular animals . They are among the oldest neurotransmitters in evolutionary terms. Tachykinin-like peptides have been found in the primitive nervous systems of cnidarians and flatworms , among others . These tachykinin-like peptides differ in their amino acid sequence in some cases significantly from the tachykinins in mammals . Tachykinins in the narrower sense with the amino acid sequence motif Gly-Leu-Met-NH 2 are also widely used . These include the majority of the vertebrate tachykinins and some invertebrate representatives. Examples of tachykinins with this sequence motif among invertebrates are the eledoisin of the octopus species Eledone aldovrandi and the sialokinins of the yellow fever mosquito .
In the human organism, tachykinins occur primarily as neurotransmitters in the nervous system. In some parts of the brain, tachykinin concentrations are in the nanomolar range. The highest concentrations were found in the substantia nigra . The tachykinins of the gastrointestinal tract are also predominantly of neuronal origin. Substance P and neurokinin A dominate here. Substance P is almost exclusively found outside the nervous system. This tachykinin is stored , among other things, in the argyrophilic cells or together with serotonin in the enterochromaffin cells . Substance P mainly functions as a tissue hormone and, after being released into the blood, reaches concentrations in the picomolar range. Tachykinins, especially substance P but also neurokinin A, are produced by some neuroendocrine tumors such as carcinoid , pheochromocytoma and small cell lung cancer .
biochemistry
structure
Tachykinins are mostly short-chain peptides that usually consist of 8 to 12 amino acids. Many of the biologically active tachykinins have the amino acid sequence Phe- (Phe / Tyr / Ile / Val) -Gly-Leu-Met-NH 2 or a related sequence.
| Tachykinin | gene | Precursor | Amino acid sequence |
|---|---|---|---|
| Substance P | TAC1 | α-, β-, γ-preprotachykinin A | Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH 2 |
| Neurokinin A | TAC1 | β-, γ-preprotachykinin A | His-Lys-Asp-Ser-Val-Phe-Gly-Leu-Met-NH 2 |
| Neuropeptide K | TAC1 | β-preprotachykinin A | Asp-Ala-Asp-Ser-Ser-Ile-Glu-Lys-Gln-Val-Ala-Leu-Leu-Lys-Ala-Leu-Tyr-Gly-His-Gly-Gln-Ile-Ser-His-Lys- Arg-His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH 2 |
| Neuropeptide γ | TAC1 | γ-preprotachykinin A | Asp-Ala-Gly-His-Gly-Gln-Ile-Ser-His-Lys-Arg-His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH 2 |
| Neurokinin B | TAC3 | Preprotachykinin B | Asp-Met-His-Asp-Phe-Phe-Val-Gly-Leu-Met-NH 2 |
| Hemokinin 1 | TAC4 | Preprotachykinin C | Thr-Gly-Lys-Ala-Ser-Gln-Phe-Phe-Gly-Leu-Met-NH 2 |
| Endokinin A. | TAC4 | Preprotachykinin C | Asp-Gly-Gly-Glu-Glu-Gln-Thr-Leu-Ser-Thr-Glu-Ala-Glu-Thr-Trp-Val-Ile-Val-Ala-Leu-Glu-Glu-Gly-Ala-Gly- Pro-Ser-Ile-Gln-Leu-Gln-Leu-Gln-Glu-Val-Lys-Thr-Gly-Lys-Ala-Ser-Gln-Phe-Phe-Gly-Leu-Met-NH 2 |
| Endokinin B | TAC4 | Preprotachykinin C | Asp-Gly-Gly-Glu-Glu-Gln-Thr-Leu-Ser-Thr-Glu-Ala-Glu-Thr-Trp-Glu-Gly-Ala-Gly-Pro-Ser-Ile-Gln-Leu-Gln- Leu-Gln-Glu-Val-Lys-Thr-Gly-Lys-Ala-Ser-Gln-Phe-Phe-Gly-Leu-Met-NH 2 |
| Endokinin C | TAC4 | Preprotachykinin C | Lys-Lys-Ala-Tyr-Gln-Leu-Glu-His-Thr-Phe-Gln-Gly-Leu-Leu-NH 2 |
| Endokinin D. | TAC4 | Preprotachykinin C | Val-Gly-Ala-Tyr-Gln-Leu-Glu-His-Thr-Phe-Gln-Gly-Leu-Leu-NH 2 |
biosynthesis
The currently known human tachykinins are indirectly encoded by three different genes . These genes , known as TAC1 , TAC3 and TAC4 , encode the precursors of tachykinins called preprotachykinins. TAC1 codes for α-, β- and γ-preprotachykinin A via an alternative splicing process . All three can be converted into substance P by enzymatic cleavage. β- and γ-preprotachykinin A contain the amino acid sequence of neurokinin A. Further cleavage products of preprotachykinins of type A are neuropeptide K and neuropeptide γ . The preprotachykinin B encoded by TAC3 is the precursor of neurokinin B. The human hemokinin 1 and the endokinins are cleavage products of the preprotachykinin C encoded by TAC4 .
function
In the human body, tachykinins play a role as neurotransmitters and tissue hormones. Thanks to different mechanisms of action, they sometimes have very different functions. Substance P plays a central role as a neurotransmitter for pain perception and pain transmission. In addition, substance P is an inflammation mediator . Its release has been linked to nausea and vomiting.
Tachykinins mediate their effects at the molecular level by stimulating the tachykinin receptors NK 1 , NK 2 and NK 3 . The human tachykinins substance P, neurokinin A and neurokinin B have a selectivity for NK 1 , NK 2 and NK 3, respectively . Upon stimulation of these receptors to the family of G-protein coupled receptors include a is signal transduction cascade starts, the activation of G proteins and the phospholipase C includes.
literature
- Severini C, Improta G, Falconieri-Erspamer G, Salvadori S, Erspamer V: The tachykinin peptide family . In: Pharmacol Rev . 54, No. 2, June 2002, pp. 285-322. PMID 12037144 .
Individual evidence
- ↑ Lecci A, Altamura M, Capriati A, Maggi CA: Tachykinin receptors and gastrointestinal motility: focus on humans . In: Eur Rev Med Pharmacol Sci . 12 Suppl 1, August 2008, pp. 69-80. PMID 18924446 .
- ↑ Page NM: Hemokinins and endokinins . In: Cell. Mol. Life Sci. . 61, No. 13, July 2004, pp. 1652-1663. doi : 10.1007 / s00018-004-4035-x . PMID 15224188 .