title: Inhibition of fibrinogen binding to human platelets by blockage of Na+/H+ exchange.
abstract: Binding of ADP to platelets enhances the binding of fibrinogen to Gp IIb-IIIa, the specific platelet receptor for adhesive proteins. The linkage between ADP and fibrinogen binding is indirect since ADP does not bind to the same receptor as fibrinogen. We have recently proposed that a third component, once affected by ADP binding, induces a conformational transition of the fibrinogen receptor from the low to the high affinity state, which is responsible for platelet aggregation [De Cristofaro, R., Landolfi, R., Castagnola, M., De Candia, E., Di Cera, E., & Wyman, J. (1988) Proc. Natl. Acad. Sci. USA 85, 8473-8476]. In the present study we provide evidence that this component should be identified with the platelet Na+/H+ antiport. Inhibition of the antiport by pharmacological agents such as amiloride, or else by decreasing extracellular Na+, results in a marked decrease of fibrinogen binding to platelets.
authors.affiliation: Istituto di Semeiotica Medica, Università Cattolica del S. Cuore, Roma, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Cristofaro
authors.forename: R
authors.initials: R
authors.lastname: Landolfi
authors.forename: E
authors.initials: E
authors.lastname: Di Cera
authors.forename: M
authors.initials: M
authors.lastname: Castagnola
authors.forename: E
authors.initials: E
authors.lastname: De Candia
authors.forename: B
authors.initials: B
authors.lastname: Bizzi
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D005340:Fibrinogen / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers
chemical_list: D002352:Carrier Proteins; D010980:Platelet Membrane Glycoproteins; D017923:Sodium-Hydrogen Exchangers; D000244:Adenosine Diphosphate; D000584:Amiloride; D005340:Fibrinogen; D001241:Aspirin