肽白三烯拮抗剂ONO - 1078对豚鼠肺中LTD4和抗原诱导的血栓素B2生成的抑制作用。

Inhibitory effect of a peptide leukotriene antagonist ONO-1078 on LTD4- and antigen-induced thromboxane B2 production in guinea pig lungs.

作者信息

Obata T, Okada Y, Nakagawa N, Terawaki T, Aishita H

机构信息

Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.

出版信息

Life Sci. 1993;52(12):PL97-102. doi: 10.1016/0024-3205(93)90201-d.

DOI:10.1016/0024-3205(93)90201-d

PMID:8445989

Abstract

The effect of a peptide leukotriene receptor antagonist ONO-1078 on the production of thromboxane (Tx) B2 induced by leukotriene (LT) D4 and antigen challenge was examined in guinea pig lungs. LTD4 (1-1,000 nM) induced a concentration-dependent production of TxB2 in non-sensitized guinea pig lungs and ovalbumin challenge (0.01-100 micrograms/ml) produced TxB2 and peptide leukotrienes in a concentration-dependent manner in ovalbumin-sensitized guinea pig lungs. ONO-1078 inhibited LTD4 (100 nM)-induced TxB2 production with the IC50 value of 0.24 microM. Furthermore, ONO-1078 inhibited antigen (10 micrograms/ml)-induced TxB2 production with the IC50 value of 0.14 microM without effect on the production of peptide leukotrienes. These results suggest that ONO-1078 may prevent the antigen-induced production of TxB2 through the blockade of the activation of receptors by endogenously generated peptide leukotrienes.

摘要

在豚鼠肺脏中研究了肽白三烯受体拮抗剂ONO - 1078对由白三烯（LT）D4和抗原激发诱导的血栓素（Tx）B2生成的影响。LTD4（1 - 1000 nM）在未致敏的豚鼠肺脏中诱导出浓度依赖性的TxB2生成，而卵清蛋白激发（0.01 - 100微克/毫升）在卵清蛋白致敏的豚鼠肺脏中以浓度依赖性方式产生TxB2和肽白三烯。ONO - 1078抑制LTD4（100 nM）诱导的TxB2生成，IC50值为0.24 microM。此外，ONO - 1078抑制抗原（10微克/毫升）诱导的TxB2生成，IC50值为0.14 microM，而对肽白三烯的生成没有影响。这些结果表明，ONO - 1078可能通过阻断内源性生成的肽白三烯对受体的激活来预防抗原诱导的TxB2生成。