Initial identification and characterization of sigma receptors on human peripheral blood leukocytes

Phencyclidine (PCP) has been reported to suppress a variety of immune functions in vitro. Because PCP binds with high affinity to both PCP and sigma receptors, the identity of the receptor(s) mediating the immunological effects of PCP is unknown. The aim of the present study was to identify and characterize the sites of PCP action (sigma and/or PCP receptors) in human peripheral blood leukocytes (PBL) using [³H]haloperidol or 1,3 di(2-[5-³H]tolyl)guanidine ([³H]DTG) to specifically label sigma receptors and 3,4-[³H]-(N)-[1-(2-thienyl)-cyclohexyl]-piperidine ([³H]TCP) to specifically label PCP receptors. [³H]Haloperidol binding was saturable and of high affinity with comparable K(D) values in human PBL (0.44 ± 0.10 nM) and rat cerebellum (0.51 ± 0.09 nM). Similarly, [³H]DTG binding was saturable with comparable K(D) values of 29.5 ± 3.5 and 26.4 ± 3.6 nM in rat cerebellum and human PBL, respectively. In contrast, there was a notable absence of [³H]TCP-labeled PCP receptors in human PBL and rat cerebellum. In competition studies, the pharmacologic profile of [³H]haloperidol-labeled sigma receptors in human PBL was virtually identical with that in rat cerebellum (slope, 0.87; correlation coefficient, 0.96); the rank order of potency of competing drugs was haloperidol > l-butaclamol = pentazocine > d-3-(hydroxyphenyl)-N-(1-propyl)-piperidine > DTG = d-butaclamol = d-SKF 10,047 > levallorphan ≥ PCP ≥ l-SKF 10,047 > TCP > MK-801. In summary, the high concentration of sigma receptors and the absence of PCP receptors on human PBL suggests that PCP may exert its immunomodulatory influence via sigma receptors. Human PBL may also represent useful peripheral markers for assessing the role of sigma receptors in the brain.