Imamichi T, Nakamura T, Hayashi K, Kaneko K, Koyama J
Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
J Pharmacobiodyn. 1990 Jun;13(6):344-52. doi: 10.1248/bpb1978.13.344.
Cinnamic acid inhibits the O2(-)-generating response of guinea pig peritoneal macrophages elicited with a chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLP), but not those with ovalbumin complex of immunoglobulin G2 antibody and phorbol-myristate acetate. During the course of study on the inhibitory mechanism of cinnamic acid, we found that the acid also inhibited the Ca2+ mobilization elicited with fMLP, but not that with the immune complex. In addition, the treatment of macrophages with Ionomycin and ethyleneglycol bis-(beta-aminoethylether)-N,N'-tetraacetic acid for depletion of the intracellular Ca2+ inactivated completely the O2- generation elicited with fMLP, but not its counterpart of the immune complex. Thus, the inhibitory activity of cinnamic acid on the O2- generation elicited with fMLP seems partly due to that on the Ca2+ mobilization. On the other hand, cinnamic acid augmented the intracellular accumulation of adenosine 3',5'-cyclic monophosphate (cyclic AMP) in the presence of 3-isobutyl 1-methylxanthine (IBMX), and elevated more intensively the concentration of cyclic AMP when macrophages were stimulated with fMLP. Since IBMX inhibited the O2- generation elicited with fMLP, the enhancement of activation of an adenylate cyclase by cinnamic acid might cause depression of the O2- generation. This possibility, however, seems to be excluded by the fact that the same effect of cinnamic acid was observed even when macrophages were stimulated with the immune complex.
肉桂酸可抑制豚鼠腹腔巨噬细胞对趋化肽N - 甲酰 - 甲硫氨酰 - 亮氨酰 - 苯丙氨酸（fMLP）产生的超氧阴离子（O₂⁻）应答，但对免疫球蛋白G2抗体与卵清蛋白复合物及佛波醇 - 肉豆蔻酸酯乙酸盐引发的应答无此作用。在研究肉桂酸的抑制机制过程中，我们发现该酸还能抑制fMLP引发的Ca²⁺动员，但对免疫复合物引发的Ca²⁺动员无抑制作用。此外，用离子霉素和乙二醇双（β - 氨基乙醚）- N,N'- 四乙酸处理巨噬细胞以耗尽细胞内Ca²⁺，可完全灭活fMLP引发的O₂⁻生成，但对免疫复合物引发的O₂⁻生成无此作用。因此，肉桂酸对fMLP引发的O₂⁻生成的抑制活性似乎部分归因于其对Ca²⁺动员的抑制作用。另一方面，在存在3 - 异丁基 - 1 - 甲基黄嘌呤（IBMX）的情况下，肉桂酸可增加细胞内3',5'- 环磷酸腺苷（环磷酸腺苷）的积累，并且当巨噬细胞受到fMLP刺激时，可更强烈地提高环磷酸腺苷的浓度。由于IBMX抑制fMLP引发的O₂⁻生成，肉桂酸对腺苷酸环化酶激活的增强可能导致O₂⁻生成的抑制。然而，即使巨噬细胞受到免疫复合物刺激时也观察到肉桂酸的相同作用，这一事实似乎排除了这种可能性。
