Effects of LG 30435 on different platelet activating factor-induced responses

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.