A possible role for extracellular bicarbonate in U-46619-induced rat platelet aggregation.
U-46619, a thromboxane A2 agonist, has been believed not to induce aggregation of rat platelets. However, we have found that U-46619 evoked rat platelet aggregation when the cells were suspended in HCO3-containing medium, whereas it was inactive in medium lacking HCO3-. 4,4'-Diisothiocyanostilbene-2,2'-disulfonate (DIDS), selective inhibitor of the HCO3/Cl- exchanger, inhibited the aggregation of rat platelets induced by U-46619 as well as by collagen and ADP. Thrombin-induced aggregation was also inhibited by DIDS, although to a much lesser extent. Several inhibitors of anion transporters, such as phloretin, pyridoxal phosphate and ethacrynic acid, suppressed U-46619-induced aggregation. These observations indicate that HCO3-influx via an anion exchanger may be involved in the signal transduction pathway of U-46619 in rat platelets.
Yokoyama
K
K
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Kudo
I
I
Nakamura
H
H
Inoue
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors; D001639:Bicarbonates / Q000494:pharmacology*; D027963:Chloride-Bicarbonate Antiporters; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D051381:Rats; D017482:Receptors, Thromboxane / Q000187:drug effects*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology
D017920:Antiporters; D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid