EFFECTS OF THIMEROSAL, AN ORGANIC SULFHYDRYL MODIFYING AGENT, ON SEROTONIN TRANSPORT ACTIVITY INTO RABBIT-BLOOD PLATELETS

The effects of the sulfhydryl group inhibitor thimerosal on serotonin (5-HT) transport activity into rabbit blood platelets were investigate d, along with its effects on the intracellular concentration of Ca2+ ( [Ca2+](i)). H-3 5-HT transport activity into rabbit blood platelets wa s inhibited by treatment with 10(-5) M thimerosal for 30 min, which di d not cause 5-HT release from platelets. The thimerosal-induced inhibi tion of 5-HT transport was antagonized by dithiothreitol. It was sugge sted that the thimerosal acts as a sulfhydryl inhibitor and inhibits 5 -HT transport activity independently of the 5-HT release reaction in o ur experiment using rabbit blood platelets. As aspirin did not affect thimerosal-induced 5-HT transport inhibition, it was suggested that th e thromboxane A(2)-generating system does not operate in the effect of thimerosal on 5-HT transport into blood platelets. Furthermore, thime rosal induced a transient elevation of [Ca2+](i), which was followed b y a sustained increase. Tn the absence of extracellular Ca2+, thimeros al caused only a transient increase in [Ca2+](i). It was suggested tha t the elevation of [Ca-2i](i) consisted of two phases, e.g. a transien t phase induced by Ca2+ mobilization from the intracellular store site s and a sustained phase which might be explained by Ca2+ influx from t he extracellular environment. In conclusion, thimerosal inhibited 5-HT transport into blood platelets at a concentration which did not induc e 5-HT release, and intracellular Ca2+ mobilization might mediate the inhibitory effect of thimerosal on 5-HT transport. (C) Copyright 1996 Elsevier Science Ltd.