The Human Platelet Dense Granule: Serotonin Uptake, Tetrabenazine Binding, Phospholipid and Ganglioside Profiles

The functioning and composition of human platelet dense granules were studied using granules purified by Percoll fractionation. Reserpine-blockable serotonin (5-HT) uptake by the dense granule fraction was characterized and also demonstrated in the crude membrane fraction. Tetrabenazine (TBZ)-displaceable [3H]ketan-serin binding was used to label the granular 5-HT transporter. Scatchard analyses, Hill plots, displacement curves, and binding kinetics indicated that TBZ-displaceable [3H]ketanserin binding labeled a site similar to that previously reported for chromaffin granules and synaptic vesicles. Analysis of phospholipid profiles in platelet fractions revealed that most platelet lysolecithin was associated with the dense granule fraction. Ganglioside analysis indicated that the predominant platelet ganglioside, GM3, was highly enriched in the dense granule fraction. The data lend further support to the idea that the 5-HT transporter complex is similar in platelet dense granules, chromaffin granules, and synaptic vesicles. However, the ganglioside and phospholipid findings clearly distinguish the types of storage sites and raise questions concerning the functional roles of dense granule GM3 and lysolecithin.