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Substance P (SP) is an 11-amino acid-long neuropeptide expressed by the central nervous system (CNS), the peripheral nervous system, and immune cells. SP is a member of the tachykinin (TAC) family of neuropeptides encoded by the TAC1 gene. SP elicits its activity via interacting with the G protein-coupled neurokinin receptors (NKRs), including NK1R, NK2R, and NK3R. NKRs are expressed on the surface of various cell types, including the blood vessels and lymphatics endothelial cells, immune cells, fibroblasts, and neurons. Activation of NKRs stimulates inositol trisphosphate/diacylglycerol (IP3/DAG) and cyclic adenosine monophosphate (cAMP) second messenger in a cell context-dependent manner. Activation of NKRs mediates complex neuronal signaling pathways linked to sensations and emotional responses. Emerging evidence suggests that substance P plays other vital roles in inflammation, wound healing, and angiogenesis. Agents that inhibit substance P activity are currently being investigated as potential drugs for pain relief and other clinical conditions.
Substance P has been implicated in the pathogenesis of several diseases.[62][63][64][54] These include the following: Emesis Fibromyalgia Eczema Psoriasis Depression Anxiety Heart failure Myocardial infarction Myocardial reperfusion injury Asthma Chronic bronchitis Inflammatory bowel diseases Migraine Osteoarthritis Rheumatoid arthritis Bipolar disorder Epilepsy Alzheimer disease Cardiomyopathies