Characterization of the stimulation of human platelets by stable analogues of PGH/sub 2//TXA/sub 2/

Thesis/Dissertation · Thu Jan 01 00:00:00 EST 1987

OSTI ID:6905252

Morinelli, T A

The specific effects of the TXA/sub 2//PGH/sub 2/ analogues, U46619 (9,11-dideoxy,9..cap alpha..-11..cap alpha..-methanoepoxy-PGF/sub 2..cap alpha../), and 9,11 aza-PGH/sub 2/, on human platelet shape change, myosin light chain phosphorylation, serotonin release, fibrinogen receptor exposure and platelet aggregation were measured and compared with binding of /sup 3/H-U46619 to platelets. Shape change and myosin light chain phosphorylation were found to saturable and dose dependent. These two effects were competitively inhibited by specific antagonists of TXA/sub 2//PGH/sub 2/ receptors (BM13177 and I-PTA-OH) indicating that they are receptor mediated. Binding of /sup 3/H-U46619 showed two components. Occupancy of high affinity binding sites correlated with platelet shape change and myosin and light chain phosphorylation. A second component with an apparent K/sub d/ of 1.46 +/- 0.47 ..mu..M, may represent a second, low-affinity site. Therefore, the platelet release reaction as not directly correlated with occupancy of high affinity receptors but could be related to the second binding component of U46619. Fibrinogen receptor exposure and platelet aggregation caused by U46619 appeared to be events mediated by the release of ADP from platelet dense granules.

• Research Organization: Temple Univ., Philadelphia, PA (USA)
• OSTI ID: 6905252
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BLOOD PLATELETS
AGGLOMERATION
CONFIGURATION INTERACTION
SHAPE
PROSTAGLANDINS
BIOLOGICAL EFFECTS
TRITIUM COMPOUNDS
DOSE-RESPONSE RELATIONSHIPS
FIBRINOGEN
PHOSPHORYLATION
RECEPTORS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION FACTORS
BODY FLUIDS
CHEMICAL REACTIONS
COAGULANTS
DRUGS
GLOBULINS
HEMATOLOGIC AGENTS
HEMOSTATICS
LABELLED COMPOUNDS
MATERIALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
PROTEINS
550301* - Cytology- Tracer Techniques