Tachykinin peptides

Tachykinins are peptides which occur as neurotransmitters and growth hormones in many animal organisms. They belong to the group of neuropeptides. Among the tachykinins include substance P, neurokinin A, neurokinin B, Hemokinin 1, Endokinin A and B. Endokinin their name from the tachykinins their ability to provide a rapid contraction of smooth muscles causing. In addition, tachykinins have effects on the nervous system, endocrine system and immune system. Their physiological effects they convey via activation of tachykinin receptors.

Occurrence

Tachykinins are widely used in the realm of multicellular animals. They belong to the evolutionarily oldest neurotransmitters. Tachykinin -like peptides have been found among others in the primitive nervous systems of cnidarians and flatworms. This tachykinin - like peptides differ in their amino acid sequence partially clear of the tachykinins in mammals. Wide dissemination have also tachykinins in the narrow sense with the amino acid sequence motif Gly -Leu -Met -NH2. These include the majority of tachykinins of vertebrates and some invertebrate representatives. Examples of tachykinins with this sequence motif among the invertebrates are the eledoisin the Krakenart Eledone Aldovrandi and Sialokinine the yellow fever mosquito.

In the human organism tachykinins are mainly found as a neurotransmitter in the nervous system. In some parts of the brain is the tachykinin concentrations in the nanomolar range. The highest concentrations were found in the substantia nigra. And the tachykinins of the gastrointestinal tract are predominantly neuronal origin. Here, substance P, and neurokinin A. dominate outside of the nervous system is almost exclusively substance P to be found. This tachykinin is stored among others in the argyrophilic cells or together with serotonin in the enterochromaffin cells. Substance P acts essentially used as a tissue hormone and reached after delivery into the blood concentrations in the picomolar range. Tachykinins, especially substance P but also neurokinin A, are produced by some neuroendocrine tumors, such as the carcinoid, pheochromocytoma and the small cell lung cancer.

Biochemistry

Structure

Tachykinins are usually short-chain peptides, which consist of typically 8 to 12 amino acids. Many of the biologically active tachykinins carry the amino acid sequence Phe- (Phe / Tyr / Ile / Val ) -Gly -Leu -Met- NH2 or a related sequence.

Biosynthesis

The currently known human tachykinins are indirectly encoded by three different genes. These genes, referred to as TAC1, TAC3 and TAC4 encode known as Präprotachykinine precursors of tachykinins. TAC1 encodes an alternative splicing of α -, β - and γ - preprotachykinin A. All three can be converted by enzymatic cleavage in substance P. β - and γ - preprotachykinin A contains the amino acid sequence of neurokinin A. more cleavage products of the type A are Präprotachykinine γ neuropeptide K and neuropeptide. The TAC3 encoded by preprotachykinin B is the precursor of neurokinin B. The human Hemokinin 1 and the Endokinine are cleavage products of the proteins encoded by preprotachykinin TAC4 C.

Function

In the human body tachykinins play a role as a neurotransmitter and growth hormones. Due to different mechanisms of action, they have some very different functions. Substance P plays a central role as a neurotransmitter of pain sensation and pain transmission. In addition, substance P is a mediator of inflammation. Its distribution is associated with nausea and vomiting.

Their effects convey tachykinins at the molecular level via stimulation of tachykinin NK1, NK2 and NK3. The human tachykinins substance P, neurokinin A and neurokinin B have a selectivity for NK1, NK2 and NK3. After stimulation of the receptors belonging to the family of G- protein-coupled receptors, a signal transduction cascade is initiated which includes the activation of G proteins, and phospholipase C.