Sigma-1 and sigma-2 sites in rat brain: comparison of regional, ontogenetic, and subcellular patterns.
Radioligand binding assay conditions were established for the selective labeling of sigma-1 and sigma-2 sites in membrane homogenates of rat brain. Selective sigma-1 assays were conducted using 5 nM(+)[3H]SKF-10,047 in the presence of 300 nM dizocilpine (MK-801). Selective sigma-2 assays were conducted using 5 nM [3H]DTG in the presence of 1 microM (+)SKF-10,047. Distributions of sigma-1 and sigma-2 binding among brain regions were found to differ. While the brain stem yields the highest level of sigma-1 binding, it yields among the lowest levels of sigma-2 binding. The reverse is true in hippocampal membranes. Different ontogenetic patterns were also observed. Sigma-2 binding decreases substantially during brain development, whereas sigma-1 binding does not vary significantly. Patterns of distribution among subcellular fractions of rat brain homogenates were found to be similar. Both sigma-1 and sigma-2 sites are most enriched in microsomal fractions, and neither is enriched in synaptosomal or mitochondrial fractions. The present results suggest that sigma-1 and sigma-2 sites are distinct entities; they do not appear to be located on a common macromolecule, and they do not represent two different affinity states of a single type of binding site. While the precise subcellular locations of sigma-1 and sigma-2 sites remain to be determined, we conclude that localization of either type of binding site to synaptic regions of plasma membrane or to mitochondria is highly unlikely.
McCann
D J
DJ
Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224.
Weissman
A D
AD
Su
T P
TP
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development* / Q000648:ultrastructure; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D000927:Anticonvulsants; D006146:Guanidines; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; C012134:SK&F 10047; D010620:Phenazocine; C050232:1,3-ditolylguanidine