Regulation of fibrinogen receptor expression on human platelets
Platelet aggregation requires the binding of fibrinogen to specific receptors on the plasma membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The authors have developed a monoclonal anti-IIb-IIIa antibody (PAC-1) that binds only to stimulated platelets and only in the presence of Ca. In order to better understand the steps leading to platelet aggregation, the authors used radiolabeled PAC-1 and fibrinogen to examine the effect of the ..cap alpha../sub 2/-adrenergic agonist, epinephrine, on the expression and function of the fibrinogen receptor. The addition of epinephrine to unstirred platelets caused and immediate increase in PAC-1 and fibrinogen binding that was associated with platelet aggregation once the platelets were stirred. Even after prolonged incubation of the platelets with epinephrine, fibrinogen receptor expression could be reversed by adding EGTA, PGl/sub 2/, or the ..cap alpha../sub 2/-adrenergic antagonist, phentolamine. When unstirred platelets were exposed to epinephrine for more than 10 min, the extent of aggregation caused by subsequent stirring was decreased by 70%. Surprisingly, these desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due to a decrease in fibrinogen receptor expression or function. These studies demonstrate that: (1) fibrinogen receptor expression is dependent on extracellular CA; (2) induction of the fibrinogen receptor by epinephrine requires the continued presence of the agonist; and (3) prolonged stimulation of the platelet by epinephrine can lead to a reduced aggregation response by a mechanism that does not involve a loss of either fibrinogen recepor expression or fibrinogen binding.
- Research Organization:
- Univ. of Pennsylvania, Philadelphia
- OSTI ID:
- 5386216
- Report Number(s):
- CONF-8604222-; TRN: 86-026533
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ADRENALINE
BIOLOGICAL EFFECTS
BLOOD PLATELETS
BLOOD COAGULATION
FIBRINOGEN
BIOCHEMICAL REACTION KINETICS
RECEPTORS
MONOCLONAL ANTIBODIES
CALCIUM
CELL MEMBRANES
GLUCOPROTEINS
LABELLED COMPOUNDS
MAN
RADIOISOTOPES
TRACER TECHNIQUES
ADRENAL HORMONES
ALKALINE EARTH METALS
ANIMALS
ANTIBODIES
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION FACTORS
BODY FLUIDS
CARBOHYDRATES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
COAGULANTS
DRUGS
ELEMENTS
GLOBULINS
HEMATOLOGIC AGENTS
HEMOSTATICS
HORMONES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
METALS
NEUROREGULATORS
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
REACTION KINETICS
SACCHARIDES
STEROID HORMONES
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques