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Increase of phosphatidylinositol arachidonic acid incorporation induced by mepacrine
N B Sterin-Speziale1, C P Setton, V L Kahane
1Department of Biological Chemistry, Buenos Aires University, Argentina.
Abstract:
In view of the fact that mepacrine (Mp) is usually used as an inhibitor of the endogenous phospholipase A2, and since this enzyme produces the release of arachidonic acid (AA) from membrane phospholipids, we studied the effect of different concentrations of Mp on the mobilization of [1-14C]AA in rat renomedullary phospholipids. During the acylation period, 0.1 mM Mp did not produce any significant change in the incorporation of [1-14C]AA into phosphatidylcholine (PC) and phosphatidylethanolamine (PE), and only a slight increase in phosphatidylinositol (PI). Higher concentrations of Mp (0.5 to 1.0 mM) produced a decrease of radioactivity in PE and PC with an increase in PI. Using prelabeled slices, a dose-dependent decrease in the 14C-radioactivity in PE and PC was observed, with a parallel increase in PI. This effect of Mp persisted even in the presence of a physiological activator of phospholipase A2, bradykinin (BK). No change in the net amount of phospholipids was observed at any of the Mp concentrations used. The results of this study show that Mp, at concentrations generally used to inhibit phospholipase A2, produced a transfer of arachidonic acid from PE and PC to PI, rather than a blockade in the release of AA from membrane phospholipids.
Insights
Mepacrine (Mp) at higher concentrations shifts arachidonic acid (AA) from phospholipids like phosphatidylcholine (PC) and phosphatidylethanolamine (PE) to phosphatidylinositol (PI). This indicates a transfer mechanism rather than a complete phospholipase A2 inhibition.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Phospholipase A2 (PLA2) enzyme releases arachidonic acid (AA) from membrane phospholipids.
- Mepacrine (Mp) is commonly used as a PLA2 inhibitor.
- Understanding AA mobilization is crucial for cellular signaling pathways.
Purpose of the Study:
- To investigate the effect of mepacrine (Mp) on arachidonic acid (AA) mobilization in rat renomedullary phospholipids.
- To determine if Mp inhibits AA release or induces a transfer between phospholipid classes.
Main Methods:
- Utilized [1-14C]AA to trace its incorporation and mobilization in rat renomedullary phospholipids.
- Administered varying concentrations of mepacrine (Mp) during acylation and to prelabeled tissue slices.
- Assessed the distribution of radioactivity in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI).
Main Results:
- Low Mp concentration (0.1 mM) showed no significant effect on [1-14C]AA incorporation into PC and PE.
- Higher Mp concentrations (0.5–1.0 mM) decreased radioactivity in PE and PC, with a concurrent increase in PI.
- This Mp-induced transfer of AA to PI occurred in a dose-dependent manner and persisted even with bradykinin (BK) stimulation.
Conclusions:
- Mepacrine (Mp), at concentrations typically used for PLA2 inhibition, promotes the transfer of arachidonic acid (AA) from PE and PC to PI.
- The findings suggest a phospholipid transfer mechanism rather than a direct blockade of AA release by PLA2.
- This highlights a more complex role for Mp in modulating lipid metabolism and signaling.