Effects of five anion channel blockers on thrombin- and ionomycin-activated platelet functions.
The inhibitory effects of anion channel blockers were evaluated on aggregation, intracellular Ca2+ rises, and the production of arachidonic acid metabolites in human platelets. Inhibitors included five anion channel blockers: phloretin, probenecid, pyridoxal phosphate, 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS). The degree of inhibition by each of these agents was dose-dependent on thrombin-activated platelet function. These agents generally had no significant inhibitory effects on ionomycin-activated platelet functions. It is suggested that anion mobilization plays a major role in the receptor-mediated activation of platelet functions, but only a minor role in Ca2+ ionophore-induced platelet activation. It is also suggested that several agents may have properties unrelated to anion channel blockers. Phloretin may be a selective cyclooxygenase inhibitor, and probenecid may inhibit phospholipase A2. DIDS and SITS may interfere with certain aggregation-inducing mechanisms.
Ozaki
Y
Y
Department of Clinical and Laboratory Medicine, Yamanashi Medical College, Japan.
Matsumoto
Y
Y
Yatomi
Y
Y
Higashihara
M
M
Kariya
T
T
Shoji
K
K
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000331:Aequorin; D001095:Arachidonic Acids / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000097:blood; D004987:Ethers / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D015759:Ionomycin; D007700:Kinetics; D010693:Phloretin / Q000494:pharmacology*; D010974:Platelet Aggregation; D011339:Probenecid / Q000494:pharmacology*; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology*; D013917:Thrombin / Q000502:physiology*
D001095:Arachidonic Acids; D004987:Ethers; D007473:Ion Channels; D013267:Stilbenes; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000331:Aequorin; D015759:Ionomycin; D011732:Pyridoxal Phosphate; D013917:Thrombin; D011339:Probenecid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D010693:Phloretin; D002118:Calcium