REGIONAL VARIATION IN THE RATIO OF SIGMA(1) TO SIGMA(2) BINDING IN RAT-BRAIN

In vitro binding experiments were performed to determine whether known subtypes of the putative sigma receptor exhibit a differential distri bution across brain regions and species. Rat brains were dissected int o nine regions, pooled, and used to prepare membranes for ligand bindi ng studies. Whole guinea pig brains were prepared in an identical mann er for comparison to rat. sigma(1) Receptors were labeled with [H-3]()-pentazocine. sigma(2) Receptors were labeled with [H-3]1,3-di-o-toly lguanidine (DTG) in the presence of 1 mu M dextrallorphan to mask sigm a(1) sites. Non-specific binding was determined in the presence of 10 mu M haloperidol. Filtration and scintillation spectroscopy provided t he binding values. The experiment revealed marked variation in the rat io of sigma(2) to sigma(1) binding across brain regions ranging from a low of 1.63 in the hindbrain to 3.51 in the cerebellum, that result m ainly differences in the density of the receptors. Scatchard analysis on membranes derived from the hindbrain and cortex suggested that the effects were due primarily to regional differences in densities of rec eptor subtypes rather than different affinities. Guinea pig brain show ed a marked preponderance of sigma(1) receptors with a ratio (sigma(2) /(s)igma(1)) of 0.67. These findings demonstrate that sigma(1) and sig ma(2) receptors are differentially distributed in rat brain.