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Histamine secretion from mast cells stimulated with ATP
1Department of Chemistry, University College London, UK.
Summary
Adenosine triphosphate (ATP) triggers histamine and prostaglandin D2 release from rat mast cells. This response is calcium-dependent and species-specific, suggesting a novel purinoceptor interaction.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Mast cells are key immune cells involved in allergic responses.
- Adenosine triphosphate (ATP) is a ubiquitous signaling molecule.
- The role of ATP in mast cell degranulation is not fully understood.
Purpose of the Study:
- To investigate the effects of Adenosine triphosphate (ATP) on mast cell degranulation.
- To identify the purinergic receptors involved in ATP-mediated mast cell responses.
- To determine the species and tissue specificity of ATP-induced mast cell mediator release.
Main Methods:
- Primary rat serosal mast cells were isolated and stimulated with ATP.
- Calcium-dependent release of histamine and prostaglandin D2 was measured.
- The effects of various antagonists (Reactive Blue 2, Suramin) and agonists were assessed.
- Responses were compared across different species (rat, guinea pig, human) and tissues.
Main Results:
- ATP induced non-cytotoxic release of histamine and prostaglandin D2 from rat mast cells.
- The release was calcium-dependent and showed significant tissue and species specificity (unresponsive in guinea pig and human mast cells).
- Antiasthmatic chromones were ineffective, while flavonoids and cAMP-active drugs inhibited the release.
- Secretion was blocked by P2Y and P2X antagonists, but not by common P2 receptor agonists.
Conclusions:
- ATP acts via a novel purinoceptor or binding site on specific mast cell types.
- This purinoceptor differs from known P2X and P2Y receptors.
- The findings have implications for understanding mast cell activation and potential therapeutic targets.