Detailed Explanation
Substance P is an 11-amino-acid neuropeptide (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH₂) belonging to the tachykinin family. It was first identified in 1931 by Ulf von Euler and John Gaddum as an uncharacterized substance in intestinal extracts that caused smooth muscle contraction — they called it 'Preparation P' (P for powder), and the name stuck. Its full sequence wasn't determined until 1971 by Michael Chang and Susan Leeman.
Substance P is one of the primary neurotransmitters in pain signaling. It is released by sensory C-fibers in the spinal cord dorsal horn, where it activates neurokinin 1 (NK1) receptors to transmit pain signals to the brain. Beyond pain, substance P mediates neurogenic inflammation (causing vasodilation, plasma extravasation, and immune cell recruitment), nausea and vomiting (via the brainstem area postrema), and mood regulation. Elevated substance P levels are associated with depression, anxiety, and inflammatory conditions.
The NK1 receptor antagonist aprepitant (Emend) was developed to block substance P and is FDA-approved as an antiemetic for chemotherapy-induced nausea and vomiting. Despite strong preclinical evidence, NK1 antagonists have largely failed as analgesics in clinical trials — one of the more frustrating disappointments in pain research, suggesting that pain transmission is more redundant than the substance P pathway alone can account for.
Key Facts
- Sequence: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH₂ (11 aa)
- Member of the tachykinin peptide family
- Discovered 1931 by von Euler and Gaddum; sequenced 1971
- Primary neurotransmitter in pain C-fiber signaling (via NK1 receptor)
- Also mediates nausea, inflammation, and mood
- NK1 antagonist aprepitant (Emend) is FDA-approved for chemotherapy nausea
- C-terminally amidated for biological activity
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PeptideDefinition.com provides educational content about peptide science. Not medical advice. Consult a licensed healthcare provider for medical decisions.