Wang J P, Hsu M F, Raung S L, Kuo S C
Department of Medical Research, Taichung Veterans General Hospital, Taiwan, Republic of China.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Mar;349(3):324-30. doi: 10.1007/BF00169300.
Like indomethacin, BW755C, diphenhydramine and methysergide, 2-phenyl-4-quinolone (YT-1) suppressed the polymyxin B-induced hind-paw edema. This inhibitory effect of YT-1 was also demonstrated in adrenalectomized mice. YT-1 inhibited the antidromic stimulation of saphenous nerve-induced plasma leakage in dorsal paw skin and reduced the volume of plasma exudation in PCA reaction. Bradykinin-, substance P- and compound 48/80-induced mouse ear edema was suppressed by YT-1 in a dose-dependent manner. In isolated rat peritoneal mast cells, YT-1 produced a dose-dependent inhibition of bradykinin-, substance P- and compound 48/80-induced histamine and beta-glucuronidase release. YT-1 also reduced the TXB2 formation from PMN leukocytes with IC50 2.0 +/- 0.5 microM, however with little effect on LTB4 formation. Histamine- and serotonin-induced plasma exudation in ear edema were reduced by YT-1. Moreover, the maximal response of ileum contraction caused by histamine and serotonin were also suppressed by YT-1 in a dose-dependent manner. In compound 48/80-pretreatment mice, YT-1 failed to suppress the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine combined with methysergide did. These results indicate that the inhibitory effect of YT-1 on local edema formation is not through the release of steroid hormones from adrenal gland, and is probably by suppressing the release of chemical mediators from mast cells, inhibition of prostaglandins formation, and noncompetitive but selective protection of the vasculature against the histamine- and serotonin-induced plasma extravasation.
与吲哚美辛、BW755C、苯海拉明和甲基麦角新碱一样，2-苯基-4-喹诺酮（YT-1）可抑制多粘菌素B诱导的后爪水肿。YT-1的这种抑制作用在肾上腺切除的小鼠中也得到了证实。YT-1抑制隐神经的逆向刺激诱导的背爪皮肤血浆渗漏，并减少PCA反应中的血浆渗出量。缓激肽、P物质和化合物48/80诱导的小鼠耳水肿被YT-1以剂量依赖性方式抑制。在分离的大鼠腹膜肥大细胞中，YT-1对缓激肽、P物质和化合物48/80诱导的组胺和β-葡萄糖醛酸酶释放产生剂量依赖性抑制。YT-1还降低了PMN白细胞中TXB2的形成，IC50为2.0±0.5微摩尔，然而对LTB4的形成影响很小。YT-1减少了组胺和5-羟色胺诱导的耳水肿中的血浆渗出。此外，组胺和5-羟色胺引起的回肠收缩的最大反应也被YT-1以剂量依赖性方式抑制。在化合物48/80预处理的小鼠中，YT-1未能比苯海拉明与甲基麦角新碱联合使用更显著地抑制缓激肽和P物质诱导的耳水肿。这些结果表明，YT-1对局部水肿形成的抑制作用不是通过肾上腺释放类固醇激素，可能是通过抑制肥大细胞释放化学介质、抑制前列腺素形成以及对组胺和5-羟色胺诱导的血浆外渗进行非竞争性但选择性的血管保护。
