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Effect of the carboxylic ionophore monensin on histamine release from rat peritoneal mast cells
G Decorti1, F Bartoli Klugmann, E Crivellato
1Institute of Pharmacology, School of Medicine, University of Trieste, Italy.
Abstract:
The effect of the monovalent carboxylic ionophore monensin, which mediates a one-for-one exchange of intracellular H+ for extracellular Na+, was investigated in purified rat peritoneal mast cells. Monensin inhibited histamine secretion induced by compound 48/80, adriamycin and the calcium ionophore A23187; the inhibitory effect was maximal when the compound was added at least 10 min before the secretagogues. Washing of cells before addition of the secretagogues did not abolish the inhibitory effect of monensin. On the contrary the carboxylic ionophore was completely ineffective in preventing concanavalin A-induced histamine release. When rat peritoneal mast cells were incubated in the presence of monensin for longer period (up to 5 hours), the substance induced a slow, progressive and dose dependent histamine release, which, at least for lower doses was noncytotoxic. The secretory effect of monensin was still present if the ionophore was washed away after 10 min of incubation, and the incubation continued in drug-free medium. Monensin stimulated histamine secretion was strictly dependent on extracellular Na+ concentrations, and independent on extracellular Ca++.
Insights
Monensin, a sodium-potassium ionophore, inhibits histamine release from mast cells triggered by various stimuli but can also induce histamine release itself. Its effects depend on extracellular sodium levels.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Mast cells are crucial immune cells involved in allergic reactions and inflammation.
- Histamine release from mast cells is a key mediator of these responses.
- Ionophores can modulate cellular ion concentrations and influence cellular functions.
Purpose of the Study:
- To investigate the effects of the ionophore monensin on histamine secretion in rat peritoneal mast cells.
- To determine the conditions under which monensin inhibits or induces histamine release.
- To elucidate the ion dependency of monensin's effects on mast cells.
Main Methods:
- Purified rat peritoneal mast cells were used.
- Monensin was added at various time points before or after secretagogues.
- Histamine secretion was measured.
- Experiments were conducted with varying extracellular Na+ and Ca++ concentrations.
Main Results:
- Monensin inhibited histamine release induced by compound 48/80, adriamycin, and A23187, with maximal inhibition when added 10 minutes prior to secretagogues.
- Monensin did not inhibit concanavalin A-induced histamine release.
- Prolonged incubation with monensin induced a dose-dependent, non-cytotoxic histamine release.
- Monensin-induced secretion was dependent on extracellular Na+ but independent of extracellular Ca++.
Conclusions:
- Monensin exhibits dual effects on mast cell histamine secretion: inhibition of certain stimuli-induced release and induction of release under specific conditions.
- The Na+/H+ exchange activity of monensin plays a role in modulating mast cell degranulation.
- Extracellular sodium concentration is critical for monensin-mediated histamine secretion.