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Relationship: 1280
Title
Opening of calcium channel, Calcium influx leads to SP (Substance P) release, Local increase of SP
Upstream event
Downstream event
Key Event Relationship Overview
AOPs Referencing Relationship
Taxonomic Applicability
Sex Applicability
Life Stage Applicability
Key Event Relationship Description
Activation of TRPA1 or TRPV1 channels in nociceptive neurons produces calcium transients which signal the neuron to release substance P, among other neuropeptides. The local effects of substance P release are collectively termed neurogenic inflammation.
Evidence Collection Strategy
Evidence Supporting this KER
Biological Plausibility
It is unknown how TRP-mediated calcium transients directly lead to substance P release but it does not conflict with known biology.
Empirical Evidence
Nociceptive neurons have been repeatedly shown to induce neurogenic inflammation in tissue by releasing substance P and other neuropeptides (Purkiss et al, 2002, Tang et al, 2008, Nakamura et al, 2012).
Uncertainties and Inconsistencies
Mechanism is not known.
Known modulating factors
Quantitative Understanding of the Linkage
Substance P release from neurons following TRPA1 or TRPV1 agonists are typically demonstrated to be dose-responsive. The sensitivity of TRP channels may be modulated by cell signaling and events mediated by calcium transients may be modulated by cell signaling events which impact signaling through G-protein, PKC, or inositol triphosphate pathways.