Characterisation of [3H]lysergic acid diethylamide binding to a 5-hydroxytryptamine receptor on human platelet membranes

Tritiated LSD binds specifically and saturably to human platelet membranes, with binding characteristics consistent with a serotonin (5-HT) receptor. The binding affinity is 0.53 nM and capacity is 57.1 fmol/mg protein in control subjects. Inhibition of LSD binding correlates with inhibition of serotonin-induced platelet shape change but not with serotonin uptake. Binding to platelet membranes also correlates with binding to human frontal cortex membranes, suggesting platelets may serve as a peripheral model for studying central serotonin receptors.

Study at a glance

Abstract

Specific binding of [3H]lysergic acid diethylamide (LSD) to human platelet membranes, as defined by 300 nM spiperone, was saturable over the concentration range of 0.25-2.5 nM [3H]LSD. At 0.5 nM [3H]LSD the half-time for association at 37 degrees C was 56 min, half-time for dissociation was 173 min, and the kinetically derived affinity was 0.24 nM. In 19 control subjects equilibrium binding studies gave an affinity of 0.53 +/- 0.02 nM (mean +/- S.E.M.) and capacity of 57.1 +/- 5.6 fmol/mg protein (mean +/- S.E.M.). The inhibition profile was consistent with that of a 5-hydroxytryptamine (5-HT) receptor. There was a significant correlation between the inhibition of [3H]LSD binding and the inhibition of 5-HT-induced shape change, but not inhibition of active platelet uptake of 5-HT. There was also a significant correlation between the inhibition of [3H]LSD binding to human platelet membranes and human frontal cortex. Platelet [3H]LSD binding may therefore be a useful model for study of peripheral and central 5-HT receptors in man.