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Granular dissolution of mast cells and histamine release by compound 48/80 in the isolated guinea-pig heart
Abstract:
It has been shown previously that guinea-pig tissues are highly resistant to the compound 48/80. Very high doses of 48/80 cause histamine release by a cytotoxic process. However, release of histamine from guinea-pig heart can be produced by concentrations of 48/80 as low as 20 micrograms/ml. In this case the mast cells show only morphological signs of matrix dissolution with no changes in the cell membrane or other intracellular organelles. These results are similar to those observed in in vitro anaphylaxis and are indicative of non-cytotoxic histamine release. Dibutyril cyclic adenosine 3', 5', monophosphate (db. cAMP) (10(-4)M) potentiated the granular matrix dissolution and histamine release produced by 48/80 in the isolated guinea-pig heart. The compound 48/80 did not release histamine in the pulmonary perfusate of guinea-pig lung even in a dose twice as much than that used in the heart.
Insights
Compound 48/80 triggers non-cytotoxic histamine release from guinea-pig hearts, potentiated by dibutyril cyclic adenosine monophosphate. Guinea-pig lungs showed resistance to this histamine release.
Area of Science:
- Pharmacology
- Cell Biology
- Immunology
Background:
- Guinea-pig tissues exhibit high resistance to compound 48/80.
- High doses of compound 48/80 induce histamine release via a cytotoxic mechanism.
- Previous research indicates varying sensitivities of different guinea-pig tissues to compound 48/80.
Purpose of the Study:
- To investigate the mechanism of histamine release from guinea-pig heart by compound 48/80.
- To explore the role of dibutyril cyclic adenosine 3', 5', monophosphate (db cAMP) in modulating this response.
- To compare the effects of compound 48/80 on guinea-pig heart and lung tissues.
Main Methods:
- Isolated guinea-pig heart and lung perfusion models were utilized.
- Compound 48/80 was administered at varying concentrations.
- Morphological analysis of mast cells and histamine quantification were performed.
- The effect of db cAMP on histamine release was assessed.
Main Results:
- Low concentrations (20 micrograms/ml) of compound 48/80 induced non-cytotoxic histamine release from guinea-pig heart, characterized by mast cell matrix dissolution without cell membrane damage.
- Dibutyril cyclic adenosine 3', 5', monophosphate (10(-4)M) potentiated both granular matrix dissolution and histamine release induced by compound 48/80 in the isolated guinea-pig heart.
- Compound 48/80 failed to induce histamine release from guinea-pig lung perfusate, even at double the concentration used for the heart.
Conclusions:
- Compound 48/80 can induce non-cytotoxic histamine release from guinea-pig heart, distinct from its cytotoxic effects at higher doses.
- Cyclic AMP signaling pathways, modulated by db cAMP, play a role in potentiating compound 48/80-induced histamine release in the heart.
- Significant differences exist in the sensitivity of guinea-pig heart and lung tissues to the histamine-releasing effects of compound 48/80.