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.