Inhibition of calcimycin-induced stimulation of cytosolic calcium in human PMN by a LTB4 receptor antagonist.
This study investigates the significance of PMN-derived LTB4 for PMN activation by using a selective LTB4 antagonist (SC 41930). Human PMN were stimulated by platelet-activating-factor (PAF, 3 microM), a receptor dependent agonist, or by calcimycin (A 23187, 10 microM), a receptor independent agonist. PMN activation was determined by LTB4 release and changes in free cytosolic Ca++ levels. Pretreatment of the PMN with SC 41930 (0.1-10 microM) caused a concentration-dependent inhibition of agonist induced rise in cytosolic Ca++ with both PAF and calcimycin. Interestingly, at the same concentrations of SC 41.930, there was a concentration-dependent inhibition of LTB4 release. Control experiments with a cell-free 5-lipoxygenase preparation did not show any direct effect of SC 41930 on the enzyme under conditions when nordihydroguiaretic acid was active. The data demonstrate a nonselective inhibition of agonist induced PMN activation by the LTB4 receptor antagonist SC 41930 and suggest that formation of endogenous LTB4 is involved in a positive feed-back loop that is required for maximum stimulation of PMN function even by a calcium ionophore.
Heckenberger
R
R
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, FRG.
Schrör
K
K
D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D018102:Receptors, Leukotriene B4
D001578:Benzopyrans; D010972:Platelet Activating Factor; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; C059950:SC 41930; D007975:Leukotriene B4; D000001:Calcimycin; D001094:Arachidonate 5-Lipoxygenase; D002118:Calcium