Competitive inhibition of tritium-labeled platelet-activating factor binding to rabbit platelet membranes by amiloride and amiloride analogs.
Amiloride and its structural analogs, ethylisopropyl amiloride, benzamil, and dichlorobenzamil, inhibit both the specific [3H]C18-PAF binding to rabbit platelet membranes and PAF-induced aggregation of gel-filtered rabbit platelets. Detailed analysis of binding inhibitions demonstrate that ethylisopropyl amiloride is a competitive inhibitor with an equilibrium dissociation constant (KB) of 23 microM. The concentration of amiloride and its analogs needed to inhibit the PAF-induced aggregation is high and there exists no correlation between their inhibitory activities of platelet aggregation and those of Na+/H+ antiporter. However, the inhibitory effects on the PAF-induced aggregation are parallel to those on the specific [3H]C18-PAF binding. The inhibitory effects of amiloride and its analogs on the activation of platelets are at the PAF-receptor binding step, rather than at the Na+/H+ antiporter.
Hwang
S B
SB
Department of Biochemical Regulation, Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065-0900.
D000584:Amiloride / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017923:Sodium-Hydrogen Exchangers; C039351:platelet activating factor receptor; D000584:Amiloride