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: Weimin Hong, Linda L Werling
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 436 Issue 1-2 Pg. 35-45 (Feb 01 2002) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11834244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cyclohexylamines
• Pyrrolidines
• Receptors, sigma
• sigma-1 receptor
• Tritium
• BD 737
• Muscarine
• Haloperidol
• Pentazocine
• Calcium

Topics

• Binding, Competitive (drug effects)
• Calcium (metabolism)
• Cyclohexylamines (metabolism, pharmacology)
• Dose-Response Relationship, Drug
• Haloperidol (metabolism)
• Humans
• Muscarine (pharmacology)
• Pentazocine (metabolism, pharmacology)
• Pyrrolidines (metabolism, pharmacology)
• Radioligand Assay
• Receptors, sigma (agonists, metabolism)
• Tritium
• Tumor Cells, Cultured