Effect of a thromboxane receptor antagonist on PGD2- and allergen-induced bronchoconstriction.
Effect of a thromboxane receptor antagonist on PGD2- and allergen-induced bronchoconstriction.
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血栓素受体拮抗剂对 PGD2 和过敏原诱导的支气管收缩的影响。
DOI：
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发表时间：
1989
影响因子：
3.3
通讯作者：
S. Holgate
中科院分区：
文献类型：
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作者：
R. Beasley;R. Featherstone;M. Church;P. Rafferty;J. Varley;A. Harris;Clive Robinson;S. Holgate
在这项研究中，我们研究了选择性强效血栓素 A2 (TxA2) 受体拮抗剂 GR32191 对 TxA2 类似物 U46619、前列腺素 (PG) D2、PGF2 α 和醋甲胆碱 (MCh) 诱导的体外豚鼠气道平滑肌收缩的影响，以及体内哮喘受试者吸入 PGD2 和 MCh 引起的气道反应。 GR32191 以相似的程度竞争性拮抗所有三种前列腺素的收缩反应，但对 MCh 诱导的收缩没有影响。在哮喘受试者中，单次口服 80 mg 剂量的 GR32191 不会影响基线气道口径或 MCh 诱导的支气管收缩，但会显着抑制 PGD2 诱导的支气管收缩，使浓度-反应曲线向右移动超过 10 倍。随后在过敏性哮喘受试者中研究了相同口服剂量的 GR32191 对过敏原诱导的立即支气管收缩的影响。在个体受试者中，GR32191 不同程度地抑制总体支气管收缩反应，最大效果发生在过敏原激发后 10 至 30 分钟之间。这些研究表明，前列腺素有助于过敏性哮喘患者吸入过敏原诱导的立即支气管收缩，并且这种作用是通过刺激血栓素受体介导的。
In this study we investigated the effect of the selective and potent thromboxane A2 (TxA2) receptor antagonist GR32191 on smooth muscle contraction induced by the TxA2 analogue U46619, prostaglandin (PG) D2, PGF2 alpha, and methacholine (MCh) in guinea pig airways in vitro and the airways response provoked by inhaled PGD2 and MCh in asthmatic subjects in vivo. GR32191 antagonized competitively the contractile responses of all three prostanoids to a similar degree but had no effect on MCh-induced contractions. In asthmatic subjects GR32191, in a single oral dose of 80 mg, did not affect base-line airway caliber or MCh-induced broncho-constriction but caused significant inhibition of PGD2-induced bronchoconstriction, displacing the concentration-response curves to the right by greater than 10-fold. The effect of the same oral dose of GR32191 on allergen-induced immediate bronchoconstriction was subsequently investigated in allergic asthmatic subjects. In individual subjects, GR32191 inhibited to varying degrees the overall bronchoconstrictor response, with the maximum effect occurring between 10 and 30 min after allergen challenge. These studies suggest that prostanoids contribute to the immediate bronchoconstriction induced by inhaled allergen in allergic asthmatics, and that this effect is mediated by stimulation of a thromboxane receptor.