title: Impaired cytoplasmic ionized calcium mobilization in inherited platelet secretion defects.
abstract: Defects in platelet cytoplasmic Ca++ mobilization have been postulated but not well demonstrated in patients with inherited platelet secretion defects. We describe studies in a 42-year-old white woman, referred for evaluation of easy bruising, and her 23-year-old son. In both subjects, aggregation and 14C-serotonin secretion responses in platelet-rich plasma (PRP) to adenosine diphosphate (ADP), epinephrine, platelet activating factor (PAF), arachidonic acid (AA), U46619, and ionophore A23187 were markedly impaired. Platelet ADP and adenosine triphosphate (ATP), contents and thromboxane synthesis induced by thrombin and AA were normal. In quin2-loaded platelets, the basal intracellular Ca++ concentration, [Ca++]i, was normal; however, peak [Ca++]i measured in the presence of 1 mmol/L external Ca++ was consistently diminished following activation with ADP (25 mumol/L), PAF (20 mumol/L), collagen (5 micrograms/mL), U46619 (1 mumol/L), and thrombin (0.05 to 0.5 U/mL). In aequorin-loaded platelets, the peak [Ca++]i studied following thrombin (0.05 and 0.5 U/mL) stimulation was diminished. Myosin light chain phosphorylation following thrombin (0.05 to 0.5 U/mL) stimulation was comparable with that in the normal controls, while with ADP (25 mumol/L) it was more strikingly impaired in the propositus. We provide direct evidence that at least in some patients with inherited platelet secretion defects, agonist-induced Ca++ mobilization is impaired. This may be related to defects in phospholipase C activation. These patients provide a unique opportunity to obtain new insights into Ca++ mobilization in platelets.
authors.affiliation: Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA.
authors.forename: A K
authors.initials: AK
authors.lastname: Rao
authors.forename: M A
authors.initials: MA
authors.lastname: Kowalska
authors.forename: J
authors.initials: J
authors.lastname: Disa
mesh_terms: D000227:Adenine Nucleotides / Q000097:blood; D000328:Adult; D000634:Aminoquinolines; D001791:Blood Platelet Disorders / Q000097:blood* / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009218:Myosins / Q000097:blood; D010766:Phosphorylation; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000302:isolation & purification; D013535:Suspensions; D013917:Thrombin / Q000494:pharmacology; D013931:Thromboxanes / Q000096:biosynthesis
chemical_list: D000227:Adenine Nucleotides; D000634:Aminoquinolines; D002250:Carbon Radioisotopes; D010980:Platelet Membrane Glycoproteins; D013535:Suspensions; D013931:Thromboxanes; C035738:Quin2-acetoxymethyl ester; D013917:Thrombin; D009218:Myosins; D002118:Calcium