title: Binding of sigma receptor ligands and their effects on muscarine-induced Ca(2+) changes in SH-SY5Y cells.
abstract: In human neuroblastoma SH-SY5Y cell preparations, sigma(1) receptor agonists (+)-pentazocine and 1S,2R-(-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine (BD737) competed for [3H]haloperidol binding with K(i) values of 67+/-10 and 14+/-10 nM, respectively. (+)-Pentazocine or BD737 up to 10 microM did not affect basal levels of intracellular Ca(2+) concentration ([Ca(2+)](i)) in these cells, but they significantly reduced muscarine-induced [Ca(2+)](i) changes in a dose-related manner. However, the reduction by (+)-pentazocine was not reversed by the sigma(1) receptor antagonist haloperidol. Further studies showed (+)-pentazocine, BD737 and haloperidol could compete for [3H]quinuclidinyl benzilate binding in SH-SY5Y cells with K(i) values of 0.51+/-0.06, 0.32+/-0.07 and 4.4+/-2.3 microM, respectively. Thus, the inhibitory effects on muscarine-induced [Ca(2+)](i) changes by (+)-pentazocine and BD737 in SH-SY5Y cells were likely due to blockade of muscarinic receptors, not due to sigma(1) receptor activation by these ligands.
authors.affiliation: Neuroscience Program, George Washington University Medical Center, 2300 I St., NW Washington, DC 20037, USA.
authors.forename: Weimin
authors.initials: W
authors.lastname: Hong
authors.forename: Linda L
authors.initials: LL
authors.lastname: Werling
mesh_terms: D001667:Binding, Competitive / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003514:Cyclohexylamines / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000378:metabolism; D006801:Humans; D009116:Muscarine / Q000494:pharmacology*; D010423:Pentazocine / Q000378:metabolism / Q000494:pharmacology*; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D017480:Receptors, sigma / Q000819:agonists* / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured; D000097605:Sigma-1 Receptor
chemical_list: D002118:Calcium; D003514:Cyclohexylamines; D006220:Haloperidol; D009116:Muscarine; D010423:Pentazocine; D011759:Pyrrolidines; D017480:Receptors, sigma; D014316:Tritium; D000097605:Sigma-1 Receptor; C075567:BD 737