Effects of MK-447 on platelet shape change, aggregation, and ATP release by collagen, ADP, and stable analogue of thromboxane A2 in rabbit platelets

Zhongguo Yao Li Xue Bao. 1999 Jul;20(7):627-30.

Abstract

Aim: To investigate the effects of MK-447 on platelet shape change, aggregation, and ATP release by collagen (Col), ADP, and stable analogue of thromboxane A2 (STA2) in rabbits.

Methods: Platelet shape change and aggregation were quantified in light transmission by turbidimetric method and release reaction was assessed by the amount of ATP in platelet-rich plasma (PRP).

Results: (1) MK-447 100-700 mumol.L-1 caused only the shape change, which was not inhibited by indometacin 3 mumol.L-1. Platelet shape changes by Col, ADP, and STA2 were reduced (P < 0.01) after the addition of MK-447. The lag phase was prolonged (P < 0.01) in Col and shortened (P < 0.01) in ADP. (2) MK-447 reduced the aggregation by Col 5 mg.L-1 (P < 0.01), and enhanced that by ADP 0.3-10 mumol.L-1 and STA2 0.1-3 mumol.L-1 (P < 0.01). (3) The release reaction by STA2 1-3 mumol.L-1 was also increased (P < 0.01). The effects of MK-447 on STA2 were not inhibited by S-145.

Conclusion: MK-447 induced the platelet shape change, and showed the dual effects, inhibition or enhancement, on the actions by different aggregating agents.

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blood Platelets / drug effects*
  • Butylated Hydroxytoluene / analogs & derivatives*
  • Butylated Hydroxytoluene / pharmacology
  • Collagen / pharmacology
  • Platelet Aggregation / drug effects*
  • Rabbits
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Butylated Hydroxytoluene
  • Thromboxane A2
  • 2-aminomethyl-4-t-butyl-6-iodophenol
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Collagen