3H-spiperone labels sigma receptors, not dopamine D2 receptors, in rat and human lymphocytes.
3H-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 3H-spiperone binding sites. In the present study we have conducted an investigation of the binding of 3H-spiperone to rat and human lymphocytes. We found that 3H-spiperone binds in a specific, saturable and reversible manner to a site in lymphocytes; however, its dissociation constant Kd (9 nM) is about 40-fold higher than in striatum. An extensive investigation of the 3H-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 3H-DTG (1,3-di-o-tolyl-guanidine), whose binding characteristics were comparable to those of sigma receptors in rat brain. Receptor density and the pharmacological profile of 3H-spiperone and 3H-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 3H-spiperone binding in these cells occurs to sigma sites and not to dopamine D2 sites.
Coccini
T
T
Department of Environmental Health, University of Washington, Seattle 98195.
Manzo
L
L
Costa
L G
LG
D000818:Animals; D001665:Binding Sites; D003342:Corpus Striatum / Q000378:metabolism; D006146:Guanidines / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid / Q000378:metabolism*; D017480:Receptors, sigma; D013134:Spiperone / Q000378:metabolism*
D006146:Guanidines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid; D017480:Receptors, sigma; D013134:Spiperone; C050232:1,3-ditolylguanidine