Sigma receptors: recent advances and new clinical potentials.
Several recent advances are leading to a better understanding of sigma receptors. Here we focus on our recent findings regarding cellular functions of sigma-2 receptors and discuss their possible clinical implications. Agonists at sigma-2 receptors induced changes in cell morphology and apoptosis in various cell types. Sigma-2 receptor activation produced both transient and sustained increases in [Ca++]i, derived from different intracellular stores. These changes in [Ca++]i and cytotoxic effects are mediated by intracellular sigma-2 receptors. Sigma-2 agonists induced apoptosis in drug-resistant cancer cells, enhanced the potency of DNA damaging agents, and down-regulated expression of p-glycoprotein mRNA. Thus, sigma-2 receptor agonists may be useful in treatment of drug-resistant cancers. Sigma radioligands have been used in tumor imaging. We also discuss how sigma-2 antagonists might prevent the irreversible motor side effects of typical neuroleptics. Sigma-2 receptors may subserve a novel signalling pathway to apoptosis, involved in regulation of cell proliferation and/or viability.
Bowen
W D
WD
Unit on Receptor Biochemistry and Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0815, USA. bowenw@bdg8.niddk.nih.gov
D000818:Animals; D006801:Humans; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000145:classification / Q000187:drug effects*; D000097605:Sigma-1 Receptor
D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor