Substance P, a powerful hypotensive agent, was the first neuropeptide ever discovered. The name derives from the fact that this molecule was an unidentified component of powder extracts from brain and intestine. Substance P is an 11-amino acid peptide present in high concentrations in the human hippocampus and neocortex. It is also released from C fibers, the small-diameter afferents in peripheral nerves that convey information about pain and temperature. Substance P is a sensory neurotransmitter in the spinal cord, where its release can be inhibited by opioid peptides released from spinal cord interneurons, resulting in the suppression of pain. The protease responsible for the inactivation of substance P is associated with synaptic membranes.

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