Subissi A, Criscuoli M
Department of Pharmacology, Laboratori Guidotti S.p.A., Pisa, Italy.
Agents Actions Suppl. 1988;23:201-6. doi: 10.1007/978-3-0348-9156-1_15.
LG 30435 is a new potential anti-asthmatic agent with multiple sites of action. It can inhibit the bronchoconstriction induced by various agonists, including platelet activating factor (PAF). The effects of this compound on PAF-induced biological responses have now been investigated. LG 30435 inhibited both serotonin release from, and aggregation of, rabbit washed platelets evoked by PAF, being four times more potent on release than on aggregation. In contrast, it did not inhibit a number of the biological effects of PAF which are not platelet-mediated, such as contraction of guinea-pig lung parenchymal strips, hypotension in rats and lethality in mice. It may be concluded that, unless platelet PAF receptors are different from those in other tissues, LG 30435 is capable of inhibiting platelet-mediated effects of PAF by interfering with secondary mechanisms activated by this autacoid and not by direct antagonism of PAF at receptor sites.
LG 30435是一种具有多个作用位点的新型潜在抗哮喘药物。它可以抑制由多种激动剂诱导的支气管收缩,包括血小板活化因子(PAF)。现已研究了该化合物对PAF诱导的生物学反应的影响。LG 30435抑制了PAF诱发的兔洗涤血小板中5-羟色胺的释放和聚集,对释放的抑制作用比对聚集的抑制作用强四倍。相比之下,它不抑制PAF的许多非血小板介导的生物学效应,例如豚鼠肺实质条的收缩、大鼠的低血压和小鼠的致死性。可以得出结论,除非血小板PAF受体与其他组织中的受体不同,LG 30435能够通过干扰这种自分泌物质激活的二级机制来抑制PAF的血小板介导效应,而不是通过在受体位点直接拮抗PAF。