title: Further characterization of [3H]ifenprodil binding in rat brain.
abstract: The present study was undertaken to characterize [3H]ifenprodil binding in rat brain. [3H]Ifenprodil showed saturable, high-affinity binding at 4 degrees C. Specific binding, defined with 10 microM ifenprodil as a competitor, was inhibited biphasically by the s receptor ligands, GBR 12909, 1,3-di-o-tolylguanidine (DTG), and (+)-3-(3-hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP). At 4 degrees C, 3 microM GBR 12909, which inhibited about 50% of specific binding of [3H]ifenprodil was used to mask sigma receptors. Under these conditions, specific binding of [3H]ifenprodil was inhibited potently by ifenprodil, SL 82.0715, poly(L-arginine), poly(L-lysine), neomycin, ruthenium red, spermine, arcaine and spermidine. In the presence of 3 microM GBR 12909, Zn2+ and Mg2+ partially inhibited specific binding of [3H]ifenprodil at 4 degrees C. In contrast, in the absence of GBR 12909, at 37 degrees C specific binding of [3H]ifenprodil was partially inhibited by Zn2+, but not by Mg2+. The anatomical distribution of [3H]ifenprodil binding at 4 degrees C (GBR 12909 included) in rat brain closely paralleled that of [3H]MK-801 (dizocilpine) binding (r = 0.971, P < 0.005). Without GBR 12909, specific [3H]ifenprodil binding at 37 degrees C was inhibited potently by sigma ligands. In the presence of 3 microM GBR 12909, [3H]ifenprodil binding at 4 degrees C was highest in synaptosomal and myelin fractions; however, without GBR 12909, [3H]ifenprodil binding at 37 degrees C was highest in microsomal and myelin fractions, consistent with the subcellular distribution of sigma receptors. The results suggest that, in the presence of 3 microM GBR 12909, at 4 degrees C, [3H]ifenprodil binds to sites that are sensitive to polyamines and related compounds; and that without GBR 12909, at 37 degrees C, [3H]ifenprodil interacts with sigma receptors in rat brain.
authors.affiliation: Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224.
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: C R
authors.initials: CR
authors.lastname: Mantione
authors.forename: M R
authors.initials: MR
authors.lastname: Spada
authors.forename: J L
authors.initials: JL
authors.lastname: Neumeyer
authors.forename: E D
authors.initials: ED
authors.lastname: London
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000378:metabolism / Q000494:pharmacology; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017480:Receptors, sigma / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D015259:Dopamine Agents; D006146:Guanidines; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D010880:Piperidines; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; C043425:vanoxerine; C026539:preclamol; C050232:1,3-ditolylguanidine; C010739:ifenprodil