Quinacrine and basic amines in human platelets: subcellular compartmentation and effects on serotonin.

Area of Science:

• Platelet biology
• Cellular pharmacology

Background:

• Human platelets contain distinct compartments for amine storage.
• Quinacrine is a fluorescent amine used to study cellular compartments.
• Platelet dense bodies and lysosomes are key storage sites for amines.

Purpose of the Study:

• To investigate the intracellular localization and effects of quinacrine in human platelets.
• To understand the mechanism of quinacrine-induced amine release from platelets.

Main Methods:

• Subcellular fractionation of human platelets.
• Quinacrine uptake and fluorescence measurements.
• Measurement of 5-hydroxytryptamine (5HT) release.
• Temperature-dependent amine efflux studies.

Main Results:

• Quinacrine accumulates in both dense bodies (61%) and lysosomes (14%) of human platelets.
• Quinacrine fluorescence is quenched within these compartments.
• Quinacrine induces 5-hydroxytryptamine (5HT) efflux from dense bodies at 37°C, but not at 0°C.
• The release mechanism appears to involve modulation of membrane permeability rather than stoichiometric exchange.

Conclusions:

• Human platelets possess multiple quinacrine-accumulating compartments, primarily dense bodies and lysosomes.
• Quinacrine's effect on 5HT release suggests a role in regulating dense body membrane permeability.
• Factors beyond pH gradients influence amine distribution within platelets.