血栓素（Tx）A2受体拮抗剂AA - 2414对U - 46619、前列腺素（PG）D2及9α，11β前列腺素F2诱导的豚鼠气管和离体人支气管收缩的抑制作用

[Inhibitory effects of AA-2414, a thromboxane (Tx) A2 receptor antagonist, on U-46619-, prostaglandin (PG) D2- and 9 alpha, 11 beta PGF2-induced contractions of guinea pig tracheas and isolated human bronchi].

作者信息

Itoh Y, Shindoh J, Horiba M, Kohno S, Ohata K, Ashida Y, Takagi K

机构信息

Department of Pneumology, Ohgaki Municipal Hospital.

出版信息

Arerugi. 1993 Nov;42(11):1670-6.

PMID:8279967

Abstract

The effects of a novel TXA2 receptor antagonist, AA-2414 [(+-)-7-(3,5,6-trimethyl-1,4-benzoquinone-2-yl)-7-phenyl-heptanoic acid], on U-46619-, PGD2- and 9 alpha, 11 beta-PGF2 alpha-induced contractions of isolated guinea pig tracheas and human bronchi were investigated. AA-2414 competitively inhibited the contractile responses of both human and guinea pig preparations induced by U-46619 with similar pA2 values (7.7 and 7.6, respectively). In addition, the compound also inhibited the contractions of both preparations caused by PGD2 and 9 alpha, 11 beta-PGF2 alpha, the IC50 values of which were 1.2 x 10(-7) and 1.8 x 10(-7) M in guinea pig tracheas and 2.8 x 10(-8) and 8.5 x 10(-8) M in human bronchi. These results suggest that AA-2414 may be a therapeutically useful drug for bronchial asthma.

摘要

研究了一种新型血栓素A2（TXA2）受体拮抗剂AA-2414[（±）-7-（3,5,6-三甲基-1,4-苯醌-2-基）-7-苯基庚酸]对U-46619、前列腺素D2（PGD2）和9α,11β-前列腺素F2α（9α,11β-PGF2α）诱导的豚鼠离体气管和人支气管收缩的影响。AA-2414以相似的pA2值（分别为7.7和7.6）竞争性抑制U-46619诱导的人和豚鼠标本的收缩反应。此外，该化合物还抑制PGD2和9α,11β-PGF2α引起的两种标本的收缩，其在豚鼠气管中的半数抑制浓度（IC50）值分别为1.2×10-7和1.8×10-7 M，在人支气管中分别为2.8×10-8和8.5×10-8 M。这些结果表明，AA-2414可能是一种对支气管哮喘有治疗作用的药物。