Binding of σ receptor ligands and their effects on muscarine-induced Ca\u3csup\u3e2+\u3c/sup\u3e changes in SH-SY5Y cells

Abstract

In human neuroblastoma SH-SY5Y cell preparations, σ1 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 Ki values of 67 ± 10 and 14 ± 10 nM, respectively. (+)-Pentazocine or BD737 up to 10 μM did not affect basal levels of intracellular Ca2+ concentration ([Ca2+]i) in these cells, but they significantly reduced muscarine-induced [Ca2+]i changes in a dose-related manner. However, the reduction by (+)-pentazocine was not reversed by the σ1 receptor antagonist haloperidol. Further studies showed (+)-pentazocine, BD737 and haloperidol could compete for [3H]quinuclidinyl benzilate binding in SH-SY5Y cells with Ki values of 0.51 ± 0.06, 0.32 ± 0.07 and 4.4 ± 2.3 μM, respectively. Thus, the inhibitory effects on muscarine-induced [Ca2+]i changes by (+)-pentazocine and BD737 in SH-SY5Y cells were likely due to blockade of muscarinic receptors, not due to σ1 receptor activation by these ligands. © 2002 Elsevier Science B.V. All rights reserved