title: Pennogenin tetraglycoside stimulates secretion-dependent activation of rat platelets: evidence for critical roles of adenosine diphosphate receptor signal pathways.
abstract: BACKGROUND
  Total steroidal saponins extracted from the rhizome of Paris polyphylla Sm. var. yunnanensis (TSSPs) have been demonstrated to promote hemostasis in vivo and induce platelet aggregation in vitro. Pennogenin tetraglycoside (Tg) has been identified as one of the active ingredients in TSSPs and can induce rat platelet aggregation.
  
  
  OBJECTIVE
  To investigate the functional role of Tg in platelets and the signaling pathway mechanisms which mediate Tg-induced platelet aggregation.
  
  
  RESULTS
  Using scanning electron microscopy, the turbidimetric method and flow cytometry, we demonstrated that Tg induces shape change and concentration-dependently induces aggregation, dense granule secretion and a-granule secretion in rat platelets. The activation characteristics were comprehensively confirmed using transmission electron microscopy. Apyrase and antagonists of the platelet adenosine diphosphate (ADP) receptors, P2Y1 and P2Y12, completely inhibited Tg-induced platelet aggregation, which was not sensitive to indomethacin or SQ29548 inhibition. Furthermore, ADP receptor antagonists inhibited Tg-induced a-granule secretion, and blockade of the P2Y1 receptor prevented Tg-induced platelet shape changes. Tg-induced dense granule secretion was not affected by ADP receptor antagonists or various various pharmacological inhibitors of the intracellular effectors involved in dense granule secretion signaling pathways.
  
  
  CONCLUSIONS
  We identified that Tg directly induces platelet activation and demonstrated that Tg-induced platelet activation depends on dense granule secretion of ADP, which in turn activates the P2Y1 and P2Y12 receptor signaling pathways.
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cong
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Liu
authors.forename: Liping
authors.initials: L
authors.lastname: Kang
authors.forename: Zuyin
authors.initials: Z
authors.lastname: Yu
authors.forename: Zhenhu
authors.initials: Z
authors.lastname: Zhao
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Baiping
authors.initials: B
authors.lastname: Ma
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Cong
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002301:Cardiac Glycosides / Q000097:blood; D008297:Male; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000097:blood*; D015398:Signal Transduction / Q000187:drug effects; D013150:Spirostans / Q000097:blood / Q000494:pharmacology*
chemical_list: D002301:Cardiac Glycosides; D018047:Receptors, Purinergic P1; D013150:Spirostans; C036302:pennogenin tetraglycoside