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

Chien-Huang Lin, Y. C. Wu, S. T. Lu, T. F. Huang, C. M. Teng

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalAsia Pacific Journal of Pharmacology
Volume7
Issue number2
Publication statusPublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

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