Preventing a shock to the system. Two-pore channel 1 negatively regulates anaphylaxis
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Updated: Dec 6, 2025

Measuring Local Anaphylaxis in Mice
Published on: October 14, 2014
Sandip Patel1, Karl-Johan Malmberg2
1Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK.
Abstract:
The mammalian two-pore channels TPC1 and TPC2 are patho-physiologically relevant endo-lysosomal cation channels regulated by the Ca2+ mobilising messenger NAADP and the phosphoinositide PI(3,5)P2. Recent work by Arlt et al shows that genetic or chemical inhibition of TPC1 in mice promotes anaphylaxis in vivo through a mechanism involving enhanced endoplasmic reticulum Ca2+ release and secretion in mast cells.
Insights
Inhibition of the TPC1 channel in mice exacerbates anaphylaxis. This occurs due to increased calcium release from the endoplasmic reticulum and enhanced mast cell secretion.
Area of Science:
- Cell Biology
- Immunology
- Physiology
Background:
- Mammalian two-pore channels TPC1 and TPC2 are endo-lysosomal cation channels.
- These channels are regulated by NAADP and PI(3,5)P2.
- TPC channels play critical roles in cellular calcium signaling.
Purpose of the Study:
- To investigate the role of TPC1 in anaphylaxis.
- To elucidate the mechanism by which TPC1 inhibition affects mast cell responses.
Main Methods:
- Genetic and chemical inhibition of TPC1 in mice.
- In vivo assessment of anaphylaxis.
- Analysis of endoplasmic reticulum calcium release and mast cell secretion.
Main Results:
- Genetic or chemical inhibition of TPC1 promotes anaphylaxis in vivo.
- TPC1 inhibition enhances endoplasmic reticulum calcium release.
- TPC1 inhibition leads to increased mast cell secretion.
Conclusions:
- TPC1 is a critical regulator of anaphylaxis.
- Inhibition of TPC1 dysregulates cellular calcium handling in mast cells, promoting allergic responses.
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