Leupeptin does not affect the normal signal transduction mechanism in platelets.
Calpains are Ca2+-dependent serine proteases that can regulate protein kinase C-mediated cellular events by cleaving the membrane-bound native enzyme to yield an activated cytosolic fragment. Inhibition of calpain by leupeptin may cause enhancement or inhibition of cellular functions depending on the nature of the protein kinase C reaction involved. We have studied the effects of leupeptin on platelet responses (aggregation, secretion, thromboxane B2 formation and intracellular Ca2+ and pH changes) induced by either thrombin, collagen or phorbol 12-myristate 13-acetate (TPA), which are known to activate protein kinase C by different mechanisms. Only thrombin-induced responses were inhibited by leupeptin. This suggests that the inhibitory effect of leupeptin is not due to antagonism of calpain in this system, but to direct interference with the proteolytic effect of thrombin.
Alonso
M T
MT
Departamento de Bioquimica y Biologia Molecular y Fisiologia, Facultad de Medicina, Universidad de Valladolid, Spain.
Sanchez
A
A
Herreros
B
B
D000255:Adenosine Triphosphate / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D012016:Reference Values; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000502:physiology; D013929:Thromboxane B2 / Q000097:blood
D007976:Leupeptins; D009842:Oligopeptides; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; D003094:Collagen; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium