PURIFICATION AND PARTIAL AMINO SEQUENCE OF A 28-KDA CYCLOPHILIN-LIKE COMPONENT OF THE RAT-LIVER SIGMA-RECEPTOR

The sigma (sigma) receptor, a putative non-opioid receptor site which has been suggested to function as a neuromodulator of dopaminergic and NMDA systems, and is found in brain, liver and many other tissues, ha s been purified > 560-fold from a detergent-solubilized rat liver memb rane preparation by affinity chromatography, using an affinity matrix prepared from an oximino derivative of haloperidol. The affinity colum n selectively retained principal components of M(r) 28 kDa, 40 kDa and 65 kDa that could be eluted from the column with sigma-selective liga nds, specifically dextrallorphan and haloperidol. After dialysis and c oncentration by ultrafiltration, a loss in density of the 65 kDa compo nent and an increase in the 28 kDa and 40 kDa components was observed. A 15 amino acid N-terminal sequence was obtained for the 28 kDa prote in which is identical to the N-terminal sequence of the 17 kDa rat cyc lophilin A, a cytosolic protein, suggesting that a critical component of the rat liver sigma receptor may be a cyclophilin. These results su pport the suggestion that sigma receptors are a key link between the c entral nervous system and the immune system.