H-3 SPIPERONE LABELS SIGMA RECEPTORS, NOT DOPAMINE D2-RECEPTORS, IN RAT AND HUMAN-LYMPHOCYTES

H-3-Spiperone binds to dopamine D2 receptors in striatum and, under the assumption that it labels the same receptors in lymphocytes, this binding site has been suggested as a biological marker for schizophrenia. Recent studies, however, have raised questions about the existence of dopamine receptor changes in drug-free schizophrenic patients, as well as on the presence and/or dopaminergic nature of lymphocytic H-3-spiperone binding sites. In the present study we have conducted an investigation of the binding of H-3-spiperone to rat and human lymphocytes. We found that H-3-spiperone binds in a specific, saturable and reversible manner to a site in lymphocytes; however, its dissociation constant K(d) (9 nM) is about 40-fold higher than in striatum. An extensive investigation of the H-3-spiperone sites indicated that their pharmacological profile was not that of a dopamine D2 site, but rather that of sigma receptors, a novel class of non-dopaminergic, non-opioid receptors which bind with high affinity antipsychotic drugs. Sigma receptors were also identified in lymphocytes using the specific ligand H-3-DTG (1,3-di-o-tolylguanidine), whose binding characteristics were comparable to those of sigma receptors in rat brain. Receptor density and the pharmacological profile of H-3-spiperone and H-3-DTG were similar. Both compounds also labelled a higher number of sites in B cells than in T cells and a good correlation was found between the lymphocytic binding of both ligands in a group of 58 people. These findings indicate that sigma receptors are present in lymphocytes and suggest that H-3-spiperone binding in these cells occurs to sigma sites and not to dopamine D2 sites.