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Substance P and Analogs
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Substance P, also known as neurokinin 1, belongs to the tachykinin neuropeptide family and is a neuropeptide that functions as a neurotransmitter and a neuromodulator. It is an 11-residue neuropeptide with the sequence Arg-Pro-Lys-Pro-Gln-Glin-Phe-Gly-Leu-Met-NH2). It is abundant in the areas of the brain responsible for regulating emotion (amygdala, periaqueductal gray matter, hypothalamus, etc.). At the same time, it is highly expressed in the cell body and nerve fibers of primary sensory neurons.
Mode of Action
Substance P is a neuropeptide widely distributed in fine nerve fibers. When the nerve is stimulated, substance P can be released at the central and peripheral terminals and play a physiological role in binding to the NK1 receptor. Substance P released at the terminal of the central end is related to the transmission of pain, and its C-terminal is involved in the transmission of pain, while the N-terminal can be reversed by naloxone. Substance P can participate in pain transmission directly or indirectly by promoting the release of glutamic acid, and its analgesic use is caused by promoting the release of encephalin. Reverse electrical stimulation of sensory nerve or axon reflex and dorsal root reflex from fine afferent fibers can slightly release substance P from the peripheral end, resulting in vasodilation and increased permeability in the dominant area of the nerve. Neurogenic inflammatory reactions such as plasma protein extravasation.
The main function of substance P is to transmit pain information-peripheral nociceptive sensation is transmitted to the spinal dorsal horn or brain stem through C-type afferent fibers, releasing substance P and glutamic acid, activating secondary nociceptive neurons. Transmit pain information to the pain center in the brain. In addition, substance P in the brain is involved in the regulation of feeling, movement and emotion, and is related to the pathogenesis of anxiety disorder, depression and schizophrenia.
1. O’Dorisio, M. S. (2018). The role of substance P, somatostatin and vasoactive intestinal peptide in modulation of mucosal immunity. In The Neuroendocrine Immune Network (pp. 187-198). CRC Press.