15-Acetylthioxy-furodysinin lactone, isolated from a marine sponge Dysidea, sp. is a potent agonist to human leukotriene B4 receptor.
A sesquiterpene thioacetate, 15-acetylthioxy-furodysinin (SK&F 105900) has been isolated from the sponge Dysidea SP. This compound can bind specifically to the human peripheral blood polymorphonuclear leukocyte (PMN) and to the differentiated human monocytic leukemic U-937 cell membrane leukotriene B4 (LTB4) receptors with high-affinity. This compound can also promote a concentration-dependent chemotaxis in PMNs and an intracellular calcium mobilization in U-937 cells that can be blocked by the LTB4 receptor antagonist, LY-223982. Furthermore, the calcium mobilization induced by SK&F 105900 can specifically cross-desensitize with the LTB4-induced calcium mobilization. These observations indicate that SK&F 105900 is a novel and specific high-affinity agonist that can bind to the LTB4 receptors and activate the receptor-mediated signal transduction processes in human PMN and U-937 cells.
Mong
S
S
Department of Immunology, SK&F Laboratories, King of Prussia, PA 19406-0939.
Votta
B
B
Sarau
H M
HM
Foley
J J
JJ
Schmidt
D
D
Carte
B K
BK
Poehland
B
B
Westley
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D006801:Humans; D007951:Leukemia, Myeloid; D007975:Leukotriene B4 / Q000378:metabolism / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D018102:Receptors, Leukotriene B4; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D012717:Sesquiterpenes; C063212:SK&F 105900; D007975:Leukotriene B4; D002118:Calcium