title: Facilitatory effects of diltiazem on dopamine release in the central nervous system. Focus on interactions with D2 autoreceptors and guanosine triphosphate binding proteins.
abstract: The purpose of the present study was to investigate the effects of a Ca antagonist (diltiazem) on dopamine release in the central nervous system. Rat striatal slices prelabeled with [3H]dopamine (DA) and superfused with Krebs-Ringer solution were stimulated electrically at a frequency of 1 Hz. Exposure to diltiazem (3.3 x 10(-7) to 1 x 10(-5) mol/L) significantly increased both the basal and stimulation-evoked [3H]DA release in a dose-dependent manner. Exogenously applied unlabeled DA inhibited the stimulation-evoked [3H]DA release. Diltiazem significantly antagonized the capacity of the unlabeled DA to inhibit stimulation-evoked [3H]DA release. The blockade of D2 receptors by a preferential D2 antagonist, sulpiride, reduced the facilitatory effect of diltiazem on stimulation-evoked [3H]DA release. Pretreatment with pertussis toxin, which interferes with the coupling of the inhibitory guanosine triphosphate-binding proteins to adenylate cyclase, significantly diminished the effects of diltiazem on stimulation-evoked [3H]DA release. These results show that diltiazem increased DA release in rat striatum, at least partially by interactions with the D2 autoreceptors and pertussis toxin-sensitive guanosine triphosphate-binding proteins.
authors.affiliation: Neurochemistry Research Laboratories, New York University Medical Center, NY.
authors.forename: K
authors.initials: K
authors.lastname: Tsuda
authors.forename: S
authors.initials: S
authors.lastname: Tsuda
authors.forename: I
authors.initials: I
authors.lastname: Nishio
authors.forename: Y
authors.initials: Y
authors.lastname: Masuyama
authors.forename: M
authors.initials: M
authors.lastname: Goldstein
mesh_terms: D037361:Adenylate Cyclase Toxin; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D004110:Diltiazem / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D019204:GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology; D014316:Tritium; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; D014316:Tritium; D013469:Sulpiride; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D004110:Diltiazem; D004298:Dopamine