title: Efficient platelet delta-granule release induced by [Ca2+]i elevation is modulated by GPIIbIIIa.
abstract: Intracellular Ca2+ elevation generates a cascade of events that leads to platelet activation and degranulation. The GPIIbIIIa-ligand molecular complex plays a central role in several aspects of platelet activation. Taking advantage of the flow cytometric simultaneous analysis of surface GPIIbIIIa expression and intracellular serotonin content, we demonstrate here that the functional inhibition of GPIIbIIIa generates an impairment of delta-granule release even upon maximal intracellular Ca2+ elevation. In healthy subjects, the GPIIbIIIa inhibitor tirofiban impairs platelet delta-granule release. Analogously, Glanzmann thrombasthenia patients show an impairment of delta-granule release that is proportional to their residual expression of platelet GPIIbIIIa. These data show that platelet surface expression of functional GPIIbIIIa is required for a fully efficient secretion of delta-granules and serotonin release. The implications of our findings are discussed in the light of the complex interplay between vesicle release and ligand-receptor triggering during platelet activation.
authors.affiliation: Department of Anatomy, Pharmacology & Forensic Medicine, Human Anatomy Section, University of Parma, Parma, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gobbi
authors.forename: Ivonne
authors.initials: I
authors.lastname: Sponzilli
authors.forename: Prisco
authors.initials: P
authors.lastname: Mirandola
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Tazzari
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.forename: Antonio
authors.initials: A
authors.lastname: Cacchioli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Matteucci
authors.forename: Gabriella
authors.initials: G
authors.lastname: Giuliani Piccari
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.forename: Marco
authors.initials: M
authors.lastname: Vitale
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D013915:Thrombasthenia / Q000097:blood
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D002118:Calcium