Inhibition by calcium channel blockers of the binding of platelet-activating factor to human neutrophil granulocytes.
The inhibitory action of calcium channel blockers on platelet-activating factor (PAF)-induced activation of human polymorphonuclear granulocytes (PMNL) and on the binding of [3H]PAF to neutrophils was studied. Verapamil and diltiazem inhibited PAF (10(-8)-10(-15) M)-induced degranulation and superoxide production in a dose-dependent manner, with pA2 values of 5.6 and 6.1 for verapamil and 5.9 and 6.2 for diltiazem, respectively. Both channel blockers inhibited the specific binding of [3H]PAF to PMNL in dose-dependent fashion, with Ki values of 3.9 +/- 0.6 X 10(-5) M and 3.2 +/- 0.4 X 10(-5) M for verapamil and diltiazem, respectively. Scatchard analysis of the binding data revealed that both calcium channel blockers decreased the receptor binding affinity and slightly increased the number of high-affinity PAF receptors, whereas they did not affect the binding affinity and number of low-affinity receptors. These results indicate that calcium channel blockers can inhibit neutrophil responses elicited by PAF by a mechanism other than inhibition of calcium influx and suggest that the PAF receptor may be closely associated with calcium channels.
Filep
J G
JG
Department of Pathophysiology, Semmelweis University Medical School, Budapest, Hungary.
Földes-Filep
E
E
D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007202:Indicators and Reagents; D010972:Platelet Activating Factor; D013481:Superoxides; D014700:Verapamil; D004110:Diltiazem