title: Sigma receptor ligands: applications in inflammation and oncology.
abstract: Sigma (sigma) receptors were initially proposed as a subtype of opiate receptors, and bind several psychoactive compounds. They are classified into sigma 1 (sigma1) and sigma 2 (sigma2) subtypes. The characterization of these subunits, and the discovery of new specific sigma receptor ligands, demonstrated that sigma receptors belong to a specific entity distinct from opiate receptors. Radioligand-binding data have recently demonstrated that the sigma1 subtype is related to a sterol isomerase, which is involved in the cholesterol biosynthesis pathway, and also to another protein of unknown function, SRBP2 (SR-31747 binding-protein 2), which shares a high homology with this enzyme. This complex group of proteins also binds molecules devoid of central effect, which demonstrate potent anti-inflammatory properties, and so are potentially useful in pathologies where pro-inflammatory cytokines are involved, particularly rheumatoid arthritis, Crohn's disease or psoriasis. In addition, the two sigma receptor subtypes and their two related proteins are also expressed on tumor cells, where they could be of prognostic relevance, and their ligands could potentially be used in the detection and targeting of tumors.
authors.affiliation: Sanofi-Synthélabo Recherche, Department of immunology and Oncology, 371 rue du Pr J Blayac, 34182 Montpellier, France. bernard.bourrie@sanofi-synthelabo.com
authors.forename: Bernard
authors.initials: B
authors.lastname: Bourrie
authors.forename: Estelle
authors.initials: E
authors.lastname: Bribes
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Derocq
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Pierre
authors.initials: P
authors.lastname: Casellas
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D008024:Ligands; D017480:Receptors, sigma / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D003510:Cyclohexanes; D007375:Interleukin-1; D008024:Ligands; D017480:Receptors, sigma; C473962:SSR125329A; D014409:Tumor Necrosis Factor-alpha; C088447:SR 31747; D000218:Adamantane