Tsai B S, Villani-Price D, Keith R H, Zemaitis J M, Bauer R F, Leonard R, Djuric S W, Shone R L
Gastrointestinal Diseases Research, G.D. Searle & Co., Skokie, IL 60077.
Prostaglandins. 1989 Dec;38(6):655-74. doi: 10.1016/0090-6980(89)90048-8.
SC-41930 was evaluated for effects on human neutrophil chemotaxis and degranulation. At concentrations up to 100 microM, SC-41930 alone exhibited no effect on neutrophil migration, but dose-dependently inhibited neutrophil chemotaxis induced by leukotriene B4 (LTB4) in a modified Boyden chamber. Concentrations of SC-41930 from 0.3 microM to 3 microM competitively inhibited LTB4-induced chemotaxis with a pA2 value of 6.35. While inactive at 10 microM against C5a-induced chemotaxis, SC-41930 inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis, with 10 times less potency than against LTB4-induced chemotaxis. SC-41930 inhibited [3H]LTB4 and [3H]fMLP binding to their receptor sites on human neutrophils with KD values of 0.2 microM and 2 microM, respectively. SC-41930 also inhibited neutrophil chemotaxis induced by 20-OH LTB or 12(R)-HETE. At concentrations up to 10 microM, SC-41930 alone did not cause neutrophil degranulation, but inhibited LTB4-induced degranulation in a noncompetitive manner. SC-41930 also inhibited fMLP- or C5a-induced degranulation, but was about 8 and 10 times less effective for fMLP and C5a, respectively. The results indicate that SC-41930 is a human neutrophil LTB4 receptor antagonist with greater specificity for LTB4 than for fMLP or C5a receptors.
对SC - 41930进行了关于其对人中性粒细胞趋化性和脱颗粒作用的评估。在浓度高达100微摩尔时，单独的SC - 41930对中性粒细胞迁移无影响，但在改良的博伊登小室中，其剂量依赖性地抑制白三烯B4（LTB4）诱导的中性粒细胞趋化性。0.3微摩尔至3微摩尔浓度的SC - 41930竞争性抑制LTB4诱导的趋化性，pA2值为6.35。虽然10微摩尔的SC - 41930对C5a诱导的趋化性无活性，但它能抑制N - 甲酰 - 甲硫氨酰 - 亮氨酰 - 苯丙氨酸（fMLP）诱导的趋化性，其效力比对LTB4诱导的趋化性低10倍。SC - 41930抑制[3H]LTB4和[3H]fMLP与人中性粒细胞上其受体位点的结合，KD值分别为0.2微摩尔和2微摩尔。SC - 41930还抑制20 - OH LTB或12（R） - HETE诱导的中性粒细胞趋化性。在浓度高达10微摩尔时，单独的SC - 41930不会引起中性粒细胞脱颗粒，但以非竞争性方式抑制LTB4诱导的脱颗粒。SC - 41930还抑制fMLP或C5a诱导的脱颗粒，但对fMLP和C5a的效力分别低约8倍和10倍。结果表明，SC - 41930是一种人中性粒细胞LTB4受体拮抗剂，对LTB4的特异性高于对fMLP或C5a受体。
