Effect of a leukotriene B4 receptor antagonist on leukotriene B4-induced neutrophil chemotaxis in cavine dermis.
Leukotriene B4 (LTB4) is a proinflammatory product of arachidonic acid metabolism that has been implicated as a mediator in a number of inflammatory diseases. When injected intradermally into the cavine. LTB4 elicits a dose-dependent immigration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-3,4-dihydro-8-p ropyl-2H- 1-benzopyran-2-carboxylic acid), a potent LTB4 receptor antagonist inhibited the chemotactic actions of LTB4 when coadministered into the dermal site and when given intravenously or orally with ED50 values of 200 ng, 0.5 mg/kg, and 0.6 mg/kg respectively. This compound may well have application in disease states, such as inflammatory bowel disease and psoriasis, where LTB4 is implicated as a proinflammatory mediator.
Fretland
D J
DJ
Department of Gastrointestinal Research, G.D. Searle and Co., Skokie, Illinois 60077.
Widomski
D L
DL
Zemaitis
J M
JM
Djurić
S W
SW
Shone
R L
RL
D000284:Administration, Oral; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006168:Guinea Pigs; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D012867:Skin / Q000166:cytology*
D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4