Abstract
Substance P (SP), an 11-amino-acid neuropeptide, has long been considered an effector of pain. However, accumulating studies have proposed a paradoxical role of SP in anti-nociception. Here, we review studies of SP-mediated nociception and anti-nociception in terms of peptide features, SP-modulated ion channels, and differential effector systems underlying neurokinin 1 receptors (NK1Rs) in differential cell types to elucidate the effect of SP and further our understanding of SP in anti-nociception. Most importantly, understanding the anti-nociceptive SP-NK1R pathway would provide new insights for analgesic drug development.
Highlights
Substance P (SP) was first described by von Euler and Gaddum, in 1931 [1]
SP preferentially binds to Neurokinin 1 (NK1) receptor (NK1R)
Full-length form is abundantly expressed in striatum, caudate nucleus, putamen, globus pallidus, nucleus accumbent, and hypothalamus; whereas the truncated NK1R expression is relatively low in the brain, and most represented in the peripheral nervous system (PNS) and peripheral tissues including heart, lung, prostate, and bone [21]
Summary
Substance P (SP) was first described by von Euler and Gaddum, in 1931 [1]. The authors observed an unknown substance that stimulated contraction of the intestine ex vivo. This substance was identified and Euler and Gaddum named it substance P, from the bottle containing it, labeled P1, P2 etc., meaning “powder”. SP belongs to the tachykinin family and serves as a neurotransmitter and a neuromodulator. It is encoded by preprotachykinin-1 (or tachykinin 1 (TAC1)) that produces SP and neurokinin A via alternative slicing and post-translational modifications [4]. The discrepant function of SP is believed to depend on the cell type regarding the expression of neurokinin receptors with unique underlying effector systems modulating differential ion channels
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