Inhibition of rabbit platelet activation in vitro by antagonists of platelet-activating factor (PAF)
The authors used washed, (/sup 3/H)serotonin-labeled rabbit platelets to study the in vitro aggregation and secretion responses induced by graded doses of PAF in the presence or absence of specific antagonists of PAF. These antagonists included CV-3988, L-652,731, triazolam and alprazolam. Platelets were pretreated with either an antagonist or the appropriate diluent for 60 sec prior to the addition of PAF (2 x 10/sup -10/ to 2 x 10/sup -7/ M). Aggregation was monitored continuously and recorded as the height of the aggregation tracing at 60 sec post-PAF. Secretion of (/sup 3/H)-serotonin was measured in a sample of the platelets removed at 60 sec post-PAF. When 2 x 10/sup -10/ M PAF was used as the stimulus, the concentration of antagonist needed for 50% inhibition (IC/sub 50/) of secretion was obtained at 0.05 ..mu..M, 0.15 ..mu..M, 0.6 ..mu..M and 2.5 ..mu..M, respectively, for L-652,731, CV-3988, triazolam and alprazolam. The corresponding IC/sub 50/ for aggregation was obtained at 0.2 ..mu..M, 0.1 ..mu..M, 1.5 ..mu..M and 6.5 ..mu..M, respectively. The inhibitory effects of these antagonists could be overcome by increasing the dose of PAF used. Although all of the antagonists were capable of completely inhibiting platelet aggregation and secretion, L-652,731 was the most potent PAF antagonist on a molar basis.
- Research Organization:
- Veterans Administration Medical Center, Oklahoma City, OK
- OSTI ID:
- 7119457
- 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. 45:4; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION
BLOOD COAGULATION FACTORS
BLOOD PLATELETS
BODY FLUIDS
COAGULANTS
DRUGS
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
INDOLES
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRROLES
RABBITS
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
SEROTONIN
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES