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 investigated, along with its effects on the intracellular concentration of Ca2+ ([Ca2+]i). 3H-5-HT transport activity into rabbit blood platelets was inhibited by treatment with 10(-5) M thimerosal for 30 min, which did not cause 5-HT release from platelets. The thimerosal-induced inhibition of 5-HT transport was antagonized by dithiotheritol. It was suggested that the thimerosal acts as a sulfhydryl inhibitor and inhibits 5-HT transport activity independently of the 5-HT release reaction in our experiment using rabbit blood platelets. As aspirin did not affect thimerosal-induced 5-HT transport inhibition, it was suggested that the thromboxane A2-generating system does not operate in the effect of thimerosal on 5-HT transport into blood platelets. Furthermore, thimerosal induced a transient elevation of [Ca2+]i, which was followed by a sustained increase. In the absence of extracellular Ca2+, thimerosal caused only a transient increase in [Ca2+]i. It was suggested that the elevation of [Ca2+]i consisted of two phases, e.g. a transient phase induced by Ca2+ mobilization from the intracellular store sites and a sustained phase which might be explained by Ca2+ influx from the extracellular environment. In conclusion, thimerosal inhibited 5-HT transport into blood platelets at a concentration which did not induce 5-HT release, and intracellular Ca2+ mobilization might mediate the inhibitory effect of thimerosal on 5-HT transport.
Nishio
H
H
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
Nezasa
K
K
Hirano
J
J
Nakata
Y
Y
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D004229:Dithiothreitol / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D011817:Rabbits; D012701:Serotonin / Q000097:blood*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D013849:Thimerosal / Q000494:pharmacology*
D011310:Preservatives, Pharmaceutical; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D013849:Thimerosal; D012701:Serotonin; D004533:Egtazic Acid; D001241:Aspirin; D002118:Calcium; D004229:Dithiothreitol