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Preferential accumulation of lithium in the dense bodies of human platelets
Insights
Lithium carbonate therapy releases significant lithium from human platelets. This suggests lithium is stored in platelet dense bodies, potentially affecting calcium levels and cell function.
Area of Science:
- Biochemistry
- Hematology
- Cell Biology
Background:
- Lithium carbonate is a common treatment for bipolar disorder.
- Platelets play a role in various physiological and pathological processes.
- The intracellular localization and storage mechanisms of lithium in platelets are not fully understood.
Purpose of the Study:
- To investigate the storage site and release mechanism of lithium in human platelets.
- To determine the effect of lithium on platelet dense bodies and their composition.
Main Methods:
- Thrombin-induced lithium release from platelets of patients on lithium therapy and normal volunteers.
- Incubation of normal platelets with lithium chloride.
- Electron microprobe analysis of platelet dense bodies.
- Analysis of synthetic dense-body core analogues.
Main Results:
- 50-73% of platelet lithium was released by thrombin in patients on lithium carbonate therapy.
- Approximately 50% of lithium was thrombin-releasable in normal platelets incubated with lithium chloride.
- Lithium was sequestered in platelet dense bodies, comprising about 10% of dense body calcium.
- Lithium addition did not alter dense body phosphorus but reduced dense body calcium by ~10%.
- Synthetic dense-body core analogues did not preferentially sequester lithium over potassium.
Conclusions:
- Lithium is primarily sequestered in human platelet dense bodies.
- The mechanism of lithium sequestration may involve selective membrane permeability rather than core binding.
- These findings shed light on lithium's interaction with platelet organelles and potential implications for its therapeutic effects.
Abstract:
From 50 to 73% of the lithium contained in platelets of patients receiving oral therapy with lithium carbonate was released by brief thrombin treatment. Similarly, about 50% of the lithium in platelets of normal volunteers incubated with lithium chloride was thrombin-releasable. The data indicate that an amount of lithium approximately equal to 10% of the calcium content was sequestered in the dense bodies (amine storage organelles) of human platelets. Electron microprobe analysis of dense bodies suggests that the addition of lithium did not change the phosphorus content but produced a loss of about 10% of the dense-body calcium. Nevertheless, synthetic solid analogues of the dense-body core incubated with lithium chloride did not sequester lithium preferentially over potassium and failed to exchange calcium for lithium. Thus, the mechanism responsible for the observed changes in platelet dense bodies may be related to selective membrane permeability properties rather than to binding of lithium to nucleotides or pyrophosphate in the dense-body core.