The mechanism of rabbit platelet aggregation induced by 2,5-di-(tert-butyl)-1,4-benzohydroquinone, an inhibitor of endoplasmic reticulum Ca2+-ATPase.
2,5-Di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), an inhibitor of endoplasmic reticulum Ca2+-ATPase, caused aggregation accompanied by a marked increase in intracellular Ca2+ concentrations ([Ca2+]i) in washed rabbit platelets. Treatment of platelets with SK&F96365 or removal of extracellular Ca2+ inhibited both Ca2+ influx and platelet aggregation induced by tBuBHQ. These responses of platelets to tBuBHQ were also inhibited by genistein. Western blots using antibody against phosphorylated amino acid residues revealed that tBuBHQ activated tyrosine kinase independently of extracellular Ca2+. These results suggest that tBuBHQ induces Ca2+ influx into platelets probably through activation of tyrosine kinase, resulting in platelet aggregation.
Furukawa
K I
KI
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Matsuzawa
M
M
Tsurufuji
S
S
Watanabe
K
K
Ohizumi
Y
Y
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000097:blood; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006873:Hydroquinones / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011817:Rabbits
D004791:Enzyme Inhibitors; D006873:Hydroquinones; D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; C019359:2,5-di-tert-butylhydroquinone; D011505:Protein-Tyrosine Kinases; D000252:Calcium-Transporting ATPases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium