Catecholamine-stimulated prostaglandin synthesis in rat brain synaptosomes [proceedings].

HT (KD = 2 x 1O-9M) and a second, saturable and reversible site of less affinity with a corresponding KD close to 2 to 3 x 10-8M. Various plotting systems ofthe binding curve indicate for the second site a positive cooperativity, the Hill coefficient being 3.7. Dissociation rates are quite high for both ligands, however it is much higher for 5-HT than for LSD; both are temperature-dependent with a respective Qlo close to 2.5 and 3. Regional distributions of binding capacities for LSD and 5-HT are very similar. They are not homogenous within the brain but vary according to the studied region, e.g. in decreasing order: striatum, hippocampus, cortex, raphe, cerebellum. Specific lesions of the tryptaminergic system have been performed by stereotaxic injections of 5-6 dihydroxytryptamine within raphe and anterior ventricles; their efficacy has been controlled by inhibition of the uptake of 5-HT. In these conditions, lesions do not modify significantly binding of one or the other ligand; this might indicate a postsynaptic location of the corresponding site. Comparative assays of the specificity of the high affinity sites for 5-HT and LSD indicate they are related to the tryptaminergic structure but some differences are observed, i.e. bromlysergamide and cyproheptadine are more efficient in displacing LSD than 5-HT (respective ID50s are 3 x 10-8 M and 6 x 10-7M for LSD, 1.5 x 10-6 and 6 x 10-6 for 5-HT). Detailed studies of interactions between 5-HT and LSD on these high affinity sites and preliminary assays involving various pretreatments of the membranes might indicate that the different sites observed correspond to an agonist and an antagonist conformation of the same 5-HT receptor-site.