API

Relationship: 1271

Title

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TRPA1 activation, TRPA1 Receptor leads to Opening of calcium channel, Calcium influx

Upstream event

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TRPA1 activation, TRPA1 Receptor

Downstream event

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Opening of calcium channel, Calcium influx

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Adjacency Weight of Evidence Quantitative Understanding
Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation adjacent High High

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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Electrophiles (e.g. isocyanates, aldehydes) react covalently with ankyrin domains while select non-reactive irritants activate through an uncharacterized alternative mechanism. Both cause localized calcium transients and deplorarization of neuronal membrane which may lead to action potentials.

Evidence Supporting this KER

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Biological Plausibility

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The basic function of TRPA1 is known and is concordant with existing biological knowledge.

Empirical Evidence

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Extensive evidence from in vitro patch clamp and in vivo toxicity studies show that TRPA1 is molecularly sensitive to electrophiles, noxious cold, and other irritants (Jordt et al, 2004, Hinman et al, 2006, Macpherson et al, 2007, Richards et al, 2010).

Uncertainties and Inconsistencies

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Some modes of TRPA1 activation are unclear.

Quantitative Understanding of the Linkage

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Threshold concentrations (EC50 values) for channel activation and action potential generation are known in the case of many TRPA1 agonists. TRPV1 sensitivity may also be regulated by various other signaling events.

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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