Tachykinin peptides

Tachykinin peptides' are a family of neuropeptides that play a crucial role in the regulation of various physiological processes in both the central and peripheral nervous systems. These peptides are characterized by their common C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X represents a variable amino acid residue. The tachykinin family includes substances such as Substance P, Neurokinin A, Neurokinin B, and others, which are involved in functions ranging from pain transmission and modulation to the regulation of blood pressure, smooth muscle contraction, and inflammatory responses.

Structure and Classification

Tachykinin peptides are derived from preprotachykinin genes through alternative splicing and proteolytic processing. There are three known preprotachykinin genes in mammals, named PPT-A, PPT-B, and PPT-C, which give rise to different tachykinins. For example, Substance P and Neurokinin A are encoded by the PPT-A gene, while Neurokinin B is encoded by the PPT-B gene.

Function

The biological activities of tachykinin peptides are mediated through their interaction with specific G protein-coupled receptors, known as tachykinin receptors. There are three main types of tachykinin receptors: NK1, NK2, and NK3, which have preferential affinity for Substance P, Neurokinin A, and Neurokinin B, respectively. Through these receptors, tachykinin peptides can exert diverse effects, including vasodilation, increased vascular permeability, stimulation of smooth muscle contraction, and modulation of pain perception.

In the central nervous system, tachykinins are involved in the regulation of mood, anxiety, stress response, and neurogenic inflammation. Peripherally, they play roles in gut motility, salivary secretion, and the modulation of the immune response.

Clinical Significance

Due to their wide range of biological activities, tachykinin peptides and their receptors have been implicated in various pathological conditions, including chronic pain, asthma, migraine, and irritable bowel syndrome. Consequently, tachykinin receptor antagonists have been explored as potential therapeutic agents for the treatment of these conditions. However, the development of clinically effective tachykinin receptor antagonists has been challenging, partly due to the complexity of tachykinin signaling and the occurrence of side effects.

Research Directions

Current research on tachykinin peptides focuses on elucidating their roles in health and disease, improving the understanding of their mechanisms of action, and developing novel therapeutic strategies targeting tachykinin receptors. This includes the design of more selective and potent tachykinin receptor antagonists and the exploration of their therapeutic potential in preclinical and clinical studies.

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