Dicentrine, a novel antiplatelet agent inhibiting thromboxane formation and increasing the cyclic AMP level of rabbit platelets

Biochem Pharmacol. 1992 Jan 22;43(2):323-9.

Abstract

Dicentrine is an antiplatelet agent isolated from the Chinese herb Lindera megaphylla. We examined the in vitro effects of dicentrine on various aspects of platelet reactivity. Dicentrine inhibited the aggregation and ATP release of washed rabbit platelets induced by arachidonic acid (AA), collagen, ADP, platelet-activating factor (PAF), thrombin and U46619. Dicentrine also inhibited the thromboxane B2 formation caused by AA, collagen and thrombin in washed intact platelets or that induced by AA in lysed platelet homogenate, while prostaglandin D2 formation caused by AA was not increased. The generation of inositol monophosphates (in the presence of indomethacin) caused by thrombin, collagen and PAF was not suppressed significantly, nor did dicentrine suppress fibrinogen-induced aggregation of elastase-treated platelets. Dicentrine inhibited the intracellular Ca2+ increase in quin-2/AM-loaded platelets caused by thrombin, PAF, collagen and AA. The cyclic AMP level was elevated by dicentrine in a concentration-dependent manner. These data indicate that the inhibitory effect of dicentrine on platelet aggregation and ATP release was due to the inhibition of thromboxane formation and the elevation of the level of cyclic AMP.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analysis
  • Alprostadil / pharmacology
  • Animals
  • Aporphines / pharmacology*
  • Arachidonic Acid / antagonists & inhibitors
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Calcium / analysis
  • Collagen / antagonists & inhibitors
  • Cyclic AMP / metabolism*
  • Inositol Phosphates / analysis
  • Phospholipids / metabolism
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Prostaglandin D2 / biosynthesis
  • Rabbits
  • Thrombin / antagonists & inhibitors
  • Thromboxane B2 / biosynthesis*

Substances

  • Aporphines
  • Inositol Phosphates
  • Phospholipids
  • Platelet Aggregation Inhibitors
  • Arachidonic Acid
  • Thromboxane B2
  • Adenosine Triphosphate
  • Collagen
  • Cyclic AMP
  • Thrombin
  • Alprostadil
  • dicentrine
  • Prostaglandin D2
  • Calcium