Effects of ergotamine and dihydroergotamine on uptake of 5-hydroxytryptamine in blood platelets

Blood platelets from healthy persons were isolated and resuspended in an artificial phosphate-buffered medium, and incubated with ergotamine and dihydroergotamine, both of which inhibited 5-HT uptake by a non-competitive mechanism.

Abstract

Blood platelets from healthy persons were isolated and resuspended in an artificial phosphate-buffered medium, and incubated with 14C-5-HT (5-hydroxytryptamine). Both ergotamine and dihydroergotamine inhibited 5-HT uptake by a non-competitive mechanism. Ergotamine was the more potent drug, giving about 50% inhibition at 10−5 M. Inhibition was also non-competitive against chloride, and was little influenced by potassium. Spontaneous efflux of 14C-5-HT was measured by incubating platelets preloaded with a small amount of 14C-5-HT in a medium with a high concentration of unlabelled 5-HT (to block reuptake of 14C-5-HT). In concentrations up to 10−5 M, neither drug had any effect on 5-HT efflux, whereas higher concentrations rapidly increased efflux. The mode of action of the drugs on the mechanism of 5-HT uptake is briefly discussed.