Histamine release from the isolated guinea-pig heart by compound 48/80
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Abstract:
Histamine release was observed in isolated guinea-pig heart perfused by the constant flow method, after bolus injection of 50-200 micrograms of compound 48/80. Practically all the histamine is released within the first 3 min after 48/80. This effect is inhibited by the addition of sodium cyanide (300 microM) to a glucose-free perfusion fluid and also by the removal of calcium of the medium in presence or absence of EDTA (100 microM). This dependence on metabolism and calcium is highly suggestive of a non-cytotoxic action of 48/80 on the mast cells of guinea-pig heart.
Insights
Compound 48/80 triggers histamine release in guinea-pig hearts. This process requires cellular metabolism and calcium, indicating a non-damaging mechanism on mast cells.
Area of Science:
- Pharmacology
- Cell Biology
- Cardiovascular Research
Background:
- Histamine release is a key mediator in allergic and inflammatory responses.
- Compound 48/80 is a known inducer of histamine release from mast cells.
- Understanding the mechanism of histamine release is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the mechanism of histamine release induced by compound 48/80 in isolated guinea-pig hearts.
- To determine the role of cellular metabolism and calcium in this process.
- To ascertain whether compound 48/80 exerts a cytotoxic effect on cardiac mast cells.
Main Methods:
- Isolated guinea-pig hearts were perfused using a constant flow method.
- Compound 48/80 was administered as a bolus injection.
- Perfusion fluid composition was altered by adding sodium cyanide or removing calcium to assess metabolic and ionic dependencies.
- Histamine levels in the perfusate were measured over time.
Main Results:
- Compound 48/80 induced rapid histamine release, with maximal release occurring within 3 minutes.
- Histamine release was significantly inhibited by sodium cyanide in a glucose-free medium, suggesting a metabolic requirement.
- Removal of calcium from the perfusion fluid, with or without EDTA, also inhibited histamine release.
- These findings suggest that compound 48/80-induced histamine release is an energy-dependent, calcium-requiring process.
Conclusions:
- Compound 48/80-induced histamine release in guinea-pig hearts is not a result of cell lysis (cytotoxicity).
- The process is dependent on cellular metabolism and extracellular calcium.
- This study supports a non-cytotoxic, active secretory mechanism for compound 48/80 action on cardiac mast cells.