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


CONCLUSIONS
MK-447 induced the platelet shape change, and showed the dual effects, inhibition or enhancement, on the actions by different aggregating agents.
Li
B Y
BY
Department of Pharmacology, Harbin Medical University, China. liby@ems.hrbmu.edu.cn
Zhou
H
H
Qiao
G F
GF
Wang
L
L
Li
W H
WH
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002084:Butylated Hydroxytoluene; D013928:Thromboxane A2; C013753:2-aminomethyl-4-t-butyl-6-iodophenol; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003094:Collagen