Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

Conference · Fri Feb 28 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5319015

Winocour, P D; Rand, M L; Kinlough-Rathbone, R L; Mustard, J F

Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with /sup 14/C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A/sub 2/ (TXA/sub 2/) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more /sup 14/C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p < 0.001; /sup 14/C release: 1.5 +/- 0.5%, p < 0.002) in response to thrombin (0.075 U/ml). Thus, a pathway independent of released ADP or TXA/sub 2/ formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of /sup 125/I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA/sub 2/ formation, the action of released ADP or increased thrombin binding.

• Research Organization: McMaster Univ., Hamilton, Ontario
• OSTI ID: 5319015
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLSALICYLIC ACID
ADP
AMINES
ANALGESICS
ANIMALS
ANTIPYRETICS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHOLESTEROL
COAGULANTS
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
HEMATOLOGIC AGENTS
HEMOSTATICS
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROXY ACIDS
HYDROXY COMPOUNDS
INDOLES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
NEUROREGULATORS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HYDROLASES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PYRROLES
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RODENTS
SENSITIVITY
SERINE PROTEINASES
SEROTONIN
STEROIDS
STEROLS
SYMPATHOMIMETICS
THROMBIN
TRACER TECHNIQUES
TRANSFERASES
TRYPTAMINES
VASCULAR DISEASES
VERTEBRATES