Molecular Pharmacology, Vol 14, 50-59, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

High-Affinity Binding of [³H]5-Hydroxytryptamine to Brain Synaptosomal Membranes: Comparison with [³H]Lysergic Acid Diethylamide Binding

¹ Laboratory of Pharmacology, Pasteur Institute, 75724 Paris Cedex 15, France

[³H]5-Hydroxytryptamine ([³H]5-HT) binds to crude brain membrane preparations at two different sites (K_d = 1-3 nM and 10-30 nM). These two sites are present in a limited number as saturable populations and selectively bind 5-HT and related structures. In the same crude membrane preparations, lysergic acid diethylamide (LSD) also binds at two different sites (K_d = 3-4 nM and 20-30 nM). 5-HT binding is found mostly in fractions enriched in synaptosomal and microsomal membranes; fractions rich in mitochondria or in synaptic vesicles have a low binding capacity. The two serotoninergic sites are physically separable; only high-affinity binding sites are found on purified synaptosomal membranes, whereas both types of sites are present in fractions enriched in microsomal membranes. The interaction between LSD and 5-HT shows that high-affinity binding sites for 5-HT are not identical with those for LSD, since the inhibition of binding of one substance by the other is complex.

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ACKNOWLEDGMENTS This investigation was supported in part by "Direction des Recherches et Moyens d'Essais (Contract No. 76/507) and Centre National de la Recherche Scientifique (A.T.P. No. 1803). We wish to thank Dr. Bocquet R., veterinaire inspecteur en chef, for his kind help in supplying horse brains.