TY - JOUR
T1 - Mechanism involved in the antiplatelet activity of naloxone in human platelets
AU - Sheu, Joen Rong
AU - Hung, Wei Chun
AU - Lee, Ling Wen
AU - Chang, Pei Te
AU - Kan, Ya Chen
AU - Yen, Mao Hsiung
PY - 1997/2/3
Y1 - 1997/2/3
N2 - In this study, naloxone was tested for its antiplatelet activity in human platelet suspensions. In platelet suspensions (4.5 x 108/ml), naloxone (0.1-0.5 mM) significantly inhibited platelet aggregation and ATP-release stimulated by various agonists (i.e., thrombin, collagen, U46619, and ADP). Furthermore, naloxone (0.5 and 0.8 mM) dose-dependently inhibited the intracellular free Ca2+ rise of Fura 2-AM loaded platelets stimulated by collagen. Additionally, naloxone (0.5 and 1.0 mM) did not influence the binding of FITC-triflavin to platelet glycoprotein (GP) IIb/IIIa complex. On the other hand, naloxone (0.5 mM) markedly decreased the fluorescence of platelet membranes tagged with diphenylhexatriene (DPH). In addition, naloxone (0.1-0.5 mM) did not significantly affect cyclic-AMP levels in human washed platelets. It is concluded that the antiplatelet activity of naloxone may possibly be due to the induction of conformational changes in the platelet membrane and the inhibition of the intracellular Ca2+ ([Ca2+]i) mobilization as well as the release reaction of platelets stimulated by agonists.
AB - In this study, naloxone was tested for its antiplatelet activity in human platelet suspensions. In platelet suspensions (4.5 x 108/ml), naloxone (0.1-0.5 mM) significantly inhibited platelet aggregation and ATP-release stimulated by various agonists (i.e., thrombin, collagen, U46619, and ADP). Furthermore, naloxone (0.5 and 0.8 mM) dose-dependently inhibited the intracellular free Ca2+ rise of Fura 2-AM loaded platelets stimulated by collagen. Additionally, naloxone (0.5 and 1.0 mM) did not influence the binding of FITC-triflavin to platelet glycoprotein (GP) IIb/IIIa complex. On the other hand, naloxone (0.5 mM) markedly decreased the fluorescence of platelet membranes tagged with diphenylhexatriene (DPH). In addition, naloxone (0.1-0.5 mM) did not significantly affect cyclic-AMP levels in human washed platelets. It is concluded that the antiplatelet activity of naloxone may possibly be due to the induction of conformational changes in the platelet membrane and the inhibition of the intracellular Ca2+ ([Ca2+]i) mobilization as well as the release reaction of platelets stimulated by agonists.
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U2 - 10.1006/bbrc.1996.6037
DO - 10.1006/bbrc.1996.6037
M3 - Article
C2 - 9070210
AN - SCOPUS:0031550555
SN - 0006-291X
VL - 231
SP - 12
EP - 16
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -