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Does intracellular histamine mediate mast cell histamine release?

L J Brandes¹, B Sukhu, R P Bogdanovic

¹Department of Medicine, University of Manitoba, Winnipeg, Canada.

Biochemical and Biophysical Research Communications

|March 16, 1990

Summary

Histamine release from mast cells is blocked by DPPE, a novel HIC antagonist. This suggests intracellular histamine, acting via HIC, mediates mast cell histamine secretion, similar to platelet responses.

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Area of Science:

Immunology
Pharmacology
Cell Biology

Background:

Histamine is known to mediate platelet aggregation and serotonin release via a novel intracellular receptor (HIC).
The HIC antagonist DPPE inhibits these platelet responses.
The mechanisms underlying histamine release from mast cells share similarities with platelet serotonin release.

Purpose of the Study:

To investigate the role of the HIC receptor in histamine release from mast cells.
To compare the efficacy of DPPE with traditional H1 and H2 antagonists in blocking mast cell histamine release.

Main Methods:

Mast cells were stimulated with concanavalin A.
Histamine release was measured in the presence of DPPE, pyrilamine (H1 antagonist), and cimetidine (H2 antagonist).

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The potency of compounds to inhibit 3H-histamine binding to rat brain membranes and liver microsomes was assessed.

Main Results:

DPPE inhibited concanavalin A-stimulated mast cell histamine release with an IC50 of 30 microM.
DPPE was more potent than pyrilamine (IC50 = 150 microM) and cimetidine (IC50 = 5 mM).
The rank order of potency for inhibiting histamine release correlated with 3H-histamine binding affinities.

Conclusions:

Histamine release from mast cells is likely mediated by intracellular histamine acting through the HIC receptor.
Mast cells may mobilize intracellular histamine from bound stores, rather than relying on newly synthesized histamine, for secretion.