Platelet-activating factor antagonism in rabbit platelets by the derivative of ochotensimine isolated from corydalis ochotensis

Dihydroochotensimine (DHO) N-oxide, the derivative of ochotensimine which was isolated from corydalis ochotensis, was investigated for its action on washed rabbit platelets. Low concentration (5-50 μg ml^-1) of DHO N-oxide inhibited selectively the aggregation of rabbit platelets induced by platelet-activating factor (PAF) in a concentration-dependent manner. High concentration (> 50 μg ml^-1) of DHO N-oxide inhibited the aggregation and ATP release caused by collagen and arachidonic acid and also slightly those by ATP. Although thrombin-induced aggregation was not affected by high concentration of DHO N-oxide, the ATP release reaction was markedly suppressed. Prolongation of the incubation time of DHO N-oxide with platelets did not cause further inhibition and the aggregability of the agent-treated platelets could be restored after washing of platelets. The concentration-response curve of PAF-induced platelet aggregation was parallelly shifted to the right by DHO N-oxide (20, 50 and 100 μg ml^-1). The pA₂ and pA₁₀ values of DHO N-oxide on PAF-induced platelet aggregation were 5.56 and 4.67, respectively, with a slope value of -1.07. High concentration of DHO N-oxide inhibited the formation of thromboxane B₂ caused by arachidonic acid, collagen and thrombin. The formation of inositol monophosphate caused by PAF was almost completely inhibited by DHO N-oxide (50 μg ml^-1) and those caused by collagen and thrombin were partially inhibited by DHO N-oxide (200 μg ml^-1). PAF-induced rise of the intracellular calcium concentration was suppressed by DHO N-oxide. It is concluded that DHO N-oxide may act as a competitive PAF antagonist at low concentration, and inhibit thromboxane formation and phosphoinositides breakdown at high concentration.