API

Relationship: 1280

Title

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Opening of calcium channel, Calcium influx leads to SP (Substance P) release, Local increase of SP

Upstream event

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Opening of calcium channel, Calcium influx

Downstream event

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SP (Substance P) release, Local increase of SP

Key Event Relationship Overview

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AOPs Referencing Relationship

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Taxonomic Applicability

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Sex Applicability

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Life Stage Applicability

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Key Event Relationship Description

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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 Supporting this KER

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Biological Plausibility

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It is unknown how TRP-mediated calcium transients directly lead to substance P release but it does not conflict with known biology.

Empirical Evidence

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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

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Mechanism is not known.

Quantitative Understanding of the Linkage

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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.

Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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