Impaired cytoplasmic ionized calcium mobilization in inherited platelet secretion defects

Journal Article · Tue Aug 01 00:00:00 EDT 1989 · Blood; (USA)

OSTI ID:5543759

Rao, A K; Kowalska, M A; Disa, J ^[1]

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1. Temple Univ. School of Medicine, Philadelphia, PA (USA)

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 {sup 14}C-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.

• OSTI ID: 5543759
• Journal Information: Blood; (USA), Vol. 74:2; ISSN 0006-4971
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CALCIUM
MEMBRANE TRANSPORT
HEMIC DISEASES
PATHOGENESIS
ADENINES
ADP
ADRENALINE
ARACHIDONIC ACID
BLOOD COAGULATION FACTORS
BLOOD PLATELETS
CARBON 14 COMPOUNDS
CELL MEMBRANES
CYTOPLASM
GLYCOPROTEINS
LIPASE
MYOSIN
PATIENTS
PHOSPHORYLATION
PROSTAGLANDINS
SEROTONIN
SUSPENSIONS
THROMBIN
TRACER TECHNIQUES
ADRENAL HORMONES
ALKALINE EARTH METALS
AMINES
ANTIMETABOLITES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CHEMICAL REACTIONS
COAGULANTS
DISEASES
DISPERSIONS
DRUGS
ELEMENTS
ENZYMES
GLOBULINS
HEMATOLOGIC AGENTS
HEMOSTATICS
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MATERIALS
MEMBRANES
METALS
MONOCARBOXYLIC ACIDS
NEUROREGULATORS
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HYDROLASES
PROTEINS
PURINES
PYRROLES
RADIOPROTECTIVE SUBSTANCES
SERINE PROTEINASES
SYMPATHOMIMETICS
TRYPTAMINES
550901* - Pathology- Tracer Techniques