Human platelet 5-hydroxytryptamine receptors: Binding of [3H]-lysergic acid diethylamide (LSD). Effects of chronic neuroleptic and antidepressant drug administration

Chronic treatment with phenothiazines and thioxanthenes enhances serotonin-induced aggregation of human platelets. Using radiolabeled LSD, researchers found that the LSD binding site on platelets is the same as the 5-HT2 receptor responsible for shape change and aggregation. In patients receiving these neuroleptics, the number of binding sites (Bmax) increased, while binding affinity decreased, possibly due to residual drug in the membrane. The increased binding capacity was not explained by this persistence. Chronic treatment 'up-regulates' platelet 5-HT2 binding sites, which may increase sensitivity to serotonin-induced aggregation. In normal subjects, desipramine treatment also increased binding site number, accompanied by a greater prolactin response to tryptophan, suggesting a link to central serotonin function.

Study at a glance

Abstract

Chronic treatment with phenothiazines and thioxanthenes has been found to enhance 5-HT-induced aggregation of human platelets. A method has been developed to study 5-HT2 receptor binding sites on platelets utilising [3H]-LSD and more recently 125I/LSD. Results are presented which suggest that the LSD binding site is indeed the 5-HT2 binding site and that the LSD binding characterises the specific receptor responsible for 5-HT-induced shape change and aggregation. In a group of patients receiving phenothiazines or thioxanthenes, the Bmax of LSD binding was increased. The mean binding affinity was decreased possibly due to a persistence of neuroleptic in the platelet membrane preparation. Analysis showed that this was not the reason why the mean binding capacity was increased. The results show that chronic phenothiazine and thioxanthene delta treatment 'up-regulates' platelet 5-HT2 binding sites and that this may be accompanied by increased sensitivity to platelet aggregation by 5-HT. In normal subjects desipramine treatment increased the Bmax of platelet LSD binding and this was accompanied by an increased prolactin response to tryptophan which is thought to be mediated by central 5-HT function.