Sigma and phencyclidine receptors in the brain-endocrine-immune axis.

We have demonstrated the absence of PCP receptors and the presence of sigma receptors in PBLs and rat pituitary, adrenal, testis, and ovary that have kinetic and pharmacologic characteristics comparable with the sigma receptor found in the CNS. The physiologic significance of the sigma receptors in the various lymphoid and endocrine tissues remains to be determined, but their presence in such high densities suggests that endogenous sigma ligands may play an important role in regulating and integrating endocrine and immune responses. Thus, in addition to their central actions, sigma agonists including PCP and SKF 10,047 may exert their immunosuppressive and endocrine effects directly through actions in the pituitary and target organs. On the other hand, the effects of selective PCP agonists on endocrine function appear to be mediated primarily through actions in brain. Furthermore, the immunologic and endocrine effects of neuroleptics such as haloperidol, which have previously been attributed primarily to actions at D2 dopamine receptors, may also be mediated via sigma receptors in brain, lymphoid, and endocrine organs. Finally, the immune and neuroendocrine systems may represent useful "windows to the brain" to assess the role of sigma and PCP receptors in the CNS.