Lu 28-179 labels a sigma(2)-site in rat and human brain.
1'-[4-[1-(4-Fluorophenyl)-1H-indol-3-yl]-1-butyl]spiro[isobenzofuran-1(3H),4'-piperidine] (Lu 28-179) or Siramesine is a sigma-ligand with high specificity for sigma(2)-sites, has been tritiated to directly label these sites in brain. [(3)H]Lu 28-179 bound in a saturable manner to homogenates prepared from rat brain or human cortices with high affinity (K(d)=2.2 and 1.1 nM, respectively) and moderate capacity (B(max)=50+/-12 and 26+/-3 fmol mg tissue(-1), respectively). The rank order of affinity for [(3)H]Lu 28-179 binding to homogenates from human and rat brain was: Lu 28-179>ifenprodil=haloperidol>1,3-di(2-tolyl)-guanidine (DTG)>(-)pentazocinez.Gt;(+)pentazocine. Using in vitro receptor autoradiography to rat brain sections [(3)H]Lu 28-179 binding was shown to be most predominant in the cerebral cortex, piriform cortex, hippocampal formation (CA1-CA3 and dentate gyrus), superior colliculus, molecular layer of the cerebellar cortex and locus coeruleus. Overall, these data are consistent with [(3)H]Lu 28-179 labelling a sigma(2)-like binding site.
Søby
Karina Krøyer
KK
Department of Molecular Pharmacology, H Lundbeck A/S, Biological Research, DK-2500, Valby, Denmark.
Mikkelsen
Jens D
JD
Meier
Eddi
E
Thomsen
Christian
C
D000368:Aged; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001667:Binding, Competitive; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007211:Indoles / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000378:metabolism*; D012044:Regression Analysis; D013141:Spiro Compounds / Q000378:metabolism*; D014316:Tritium
D007211:Indoles; C109644:Lu 28-179; D017480:Receptors, sigma; D013141:Spiro Compounds; D014316:Tritium