Effect of ticlopidine ex vivo on platelet intracellular calcium mobilization

Journal Article · Fri Apr 01 00:00:00 EST 1988 · Thromb. Res.; (United States)

DOI:https://doi.org/10.1016/0049-3848(88)90175-2· OSTI ID:7076093

Derian, C K; Friedman, P A

The antiplatelet compound ticlopidine exerts its potent inhibitory activity through an as yet undetermined mechanism(s). The goal of this study was to determine the effect, if any, of ticlopidine ex vivo on platelet calcium mobilization. Ticlopidine inhibited ADP-induced platelet aggregation by 50-80%. In the presence of 1 mM EGTA, ticlopidine inhibited ADP- and thrombin-stimulated increases in (Ca2+)i in fura-2 loaded platelets. We evaluated further the effect of ticlopidine on calcium mobilization by examining both agonist-stimulated formation of inositol trisphosphate in intact platelets and the ability of inositol trisphosphate to release /sup 45/Ca from intracellular sites in permeabilized cells. We show here that while ticlopidine significantly affected agonist-induced intracellular calcium mobilization in intact platelets, the drug was without effect on agonist-stimulated formation of inositol trisphosphate in intact platelets and on inositol trisphosphate-induced /sup 45/Ca release in saponin-permeabilized platelets. Our study demonstrates that ticlopidine exerts at least part of its effect via inhibition of intracellular calcium mobilization but that its site of action remains to be determined.

• Research Organization: Merck Sharp and Dohme Research Laboratories, West Point, PA (USA)
• OSTI ID: 7076093
• Journal Information: Thromb. Res.; (United States), Vol. 50:1
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BLOOD PLATELETS
BLOOD COAGULATION
CALCIUM
MEMBRANE TRANSPORT
PYRIDINE
BIOLOGICAL EFFECTS
CALCIUM 45
INHIBITION
INOSITOL
RABBITS
TRACER TECHNIQUES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METALS
ANIMALS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CALCIUM ISOTOPES
CARBOHYDRATES
DAYS LIVING RADIOISOTOPES
ELEMENTS
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
INOSITOLS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MATERIALS
METALS
MONOSACCHARIDES
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIDINES
RADIOISOTOPES
SACCHARIDES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques