Calcium ionophore A23187 (Eli Lilly): effect on platelet function, structure and metabolism

Area of Science:

• Biochemistry
• Cell Biology
• Hematology

Background:

• Platelets play a crucial role in hemostasis and thrombosis.
• The platelet release reaction is a key process involving the secretion of granule contents.
• Calcium ions are known to be involved in platelet activation.

Purpose of the Study:

• To investigate the effects of ionophore A23187 on washed human platelets.
• To elucidate the role of intracellular calcium in triggering the platelet release reaction.
• To examine the metabolic and structural consequences of ionophore-induced calcium influx.

Main Methods:

• Washed human platelets were incubated in citrated saline.
• Ionophore A23187 was added at varying concentrations.
• Serotonin release, calcium influx, adenine nucleotide metabolism, and platelet ultrastructure were analyzed.

Main Results:

• Low ionophore concentrations caused serotonin release and inosine monophosphate accumulation without significant calcium influx or structural changes.
• Increasing ionophore concentration led to substantial calcium influx, altered platelet ultrastructure, and conversion of adenine nucleotides to inosine monophosphate.
• High calcium concentrations or omission of citrate exacerbated metabolic changes and caused cytoplasmic leakage.
• A weak chelator prevented cell destruction but not metabolic toxicity in the absence of divalent cations.

Conclusions:

• Intracellularly bound calcium appears to trigger the platelet release reaction.
• High ionophore concentrations exert toxic effects on platelets, impacting metabolism and structure.
• Chelators can protect platelets from ionophore-induced destruction but not metabolic toxicity.