Inhibition by the LTD4 antagonist, SR2640, of effects of LTD4 on canine polymorphonuclear leukocyte functions.
The sulfidopeptide leukotriene LTD4 selectively inhibited directed migration of canine polymorphonuclear leukocytes towards LTB4 (100 nM) with an IC50 of 38 nM. No effect on PAF-acether induced migration was observed. LTD4 did not cause detectable adherence of cells to the Boyden chamber system. Neither LTD4 nor the LTD4/LTE4 receptor antagonist, SR2640, possessed chemokinetic properties. LTD4 induced reversible aggregation of the cells with an EC50 of 36 nM. SR2640 suppressed or abolished LTD4 responses in vitro and following oral administration of the drug. SR2640 had no effect on aggregation induced by LTB4 or PAF-acether. The results can be taken as evidence that canine polymorphonuclear leukocytes possess LTD4 receptors that may be involved in a leukotriene specific micro-feedback system between the different cell types involved in inflammatory responses.
Thomsen
M K
MK
Department of Pharmacology, Leo Pharmaceutical Products, Ballerup, Denmark.
Ahnfelt-Rønne
I
I
D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000187:drug effects; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000037:antagonists & inhibitors* / Q000378:metabolism
D011804:Quinolines; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; C059177:SR 2640