Calcium-dependent displacement of haloperidol-sensitive sigma receptor binding in rat hippocampal slices following tissue depolarization.
To evaluate the possible existence of an endogenous ligand for the haloperidol-sensitive sigma receptor, we developed an in vitro competition assay to measure endogenous ligand release. Depolarization of in vitro hippocampal slices by either veratridine or potassium reduced [3H]ditolylguanidine binding in a calcium-dependent and transient manner. None of the drugs or iron substitutions directly affected [3H]ditolylguanidine binding to rat brain membranes. Veratridine-induced depolarization also reduced the binding of [3H](+)3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, another sigma radioligand, in a calcium-dependent manner. Radioligand displacement was not associated with alteration in sigma receptor dissociation kinetics or receptor degradation in the hippocampal slice. In contrast, KC1 depolarization had no effect on [3H]ditolyguanidine binding to sigma receptors in liver slices. The results suggest that a calcium-dependent, depolarization-induced reduction in sigma receptor binding may have been caused by the release of an endogenous sigma ligand in rat hippocampal tissue.
Neumaier
J F
JF
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
Chavkin
C
C
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
D006146:Guanidines; D011957:Receptors, Opioid; D014701:Veratridine; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D002118:Calcium