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The release of morphine from the mast cells by 48/80 in morphine perfused dogs
Abstract:
The aim of this study was to determine whether or not mast cells store or bind morphine. Injection of a potent mast cell depleter, compound 48/80 to dogs, 10 minutes after completion of a perfusion of 30 mg/kg of morphine produced a large concomitant increase of both morphine and histamine in blood samples drawn from the aorta. This increase is transient and statistically significant up to 1 minute following the injection of the drug. Morphine and histamine levels decrease rapidly as they reach the general circulation and are subjected to distribution. Injection of compound 48/80 one hour after the end of the morphine perfusion produces a less prominent increase in morphine and histamine levels. In both instances, subsequent doses of compound 48/80 failed to produce any increase in the levels of morphine or histamine. All these findings strongly indicate that in these dogs, the increase in morphine levels following 48/80 injection is caused by a release of morphine, bound or stored in the mast cells of the lungs, during the course of the perfusion.
Insights
This study investigated if mast cells store morphine. Results show compound 48/80 releases morphine from mast cells in dogs, indicating a transient binding or storage mechanism.
Area of Science:
- Pharmacology
- Cell Biology
Background:
- Mast cells are known to store and release histamine.
- The interaction of opioids with mast cells is not fully understood.
Purpose of the Study:
- To investigate the potential role of mast cells in storing or binding morphine.
- To determine if mast cell degranulation affects circulating morphine levels.
Main Methods:
- Dogs were perfused with morphine (30 mg/kg).
- Compound 48/80, a mast cell degranulator, was injected at different time points post-perfusion.
- Morphine and histamine levels in aortic blood were measured.
Main Results:
- A rapid, transient increase in blood morphine and histamine was observed after compound 48/80 injection shortly after morphine perfusion.
- This effect diminished when compound 48/80 was administered later.
- Subsequent doses of compound 48/80 had no significant effect.
Conclusions:
- Findings suggest that mast cells in dogs can bind or store morphine during perfusion.
- Compound 48/80-induced degranulation releases this stored morphine.
- This highlights a potential mechanism for morphine interaction with mast cells.