Phencyclidine and related compounds evoked [3H]dopamine release from rat mesencephalic cell cultures by a mechanism independent of the phencyclidine receptor, sigma binding site, or dopamine uptake site.
At concentrations greater than or equal to 100 microM, phencyclidine (PCP), N-(1-(2-thienyl)-cyclohexyl)piperidine (TCP), and MK-801 induced [3H]dopamine release from dissociated cell cultures of rat mesencephalon. This release was Ca2+ independent and tetrodotoxin insensitive. Tetrodotoxin (2 microM) itself had no effect on spontaneous release of [3H]dopamine. [3H]Dopamine release was induced by 1,3-di(2-tolyl)guanidine, a sigma ligand, and by 4-aminopyridine (1-3 mM), a K+ channel blocker. No stereoselectivity was observed for [3H]dopamine release evoked by the dioxadrol enantiomers, dexoxadrol, and levoxadrol, or by enantiomers of N-allylnormetazocine (SKF 10,047). The selective dopamine uptake inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12909) did not affect spontaneous or TCP-evoked [3H]dopamine release. Together, these data suggest that the dopamine-releasing effects of PCP-like compounds on the mesencephalic cells were not mediated by actions at the PCP receptor or sigma binding site, Ca2+, or Na+ channels, or at the high affinity dopamine uptake site. It remains conceivable that blocking actions of PCP-like compounds at voltage-regulated K+ channels may at least partly explain the response. These results are discussed in comparison with findings in intact brain.
Mount
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Douglas Hospital Research Center, Department of Pharmacology and Therapeutics, McGill University, Verdun, Quebec, Canada.
Boksa
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Chaudieu
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Quirion
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001665:Binding Sites; D002478:Cells, Cultured; D004148:Dioxolanes / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017981:Receptors, Neurotransmitter / Q000502:physiology; D017478:Receptors, Phencyclidine; D012808:Sigma Factor / Q000378:metabolism*; D014316:Tritium
D000927:Anticonvulsants; D004148:Dioxolanes; D006146:Guanidines; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D012808:Sigma Factor; D014316:Tritium; C005840:dioxadrol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C579649:levoxadrol; C012058:tenocyclidine; C043425:vanoxerine; D010622:Phencyclidine; C579650:dexoxadrol; C050232:1,3-ditolylguanidine; D004298:Dopamine