Facilitatory effects of diltiazem on dopamine release in the central nervous system. Focus on interactions with D2 autoreceptors and guanosine triphosphate binding proteins.
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.
Tsuda
K
K
Neurochemistry Research Laboratories, New York University Medical Center, NY.
Tsuda
S
S
Nishio
I
I
Masuyama
Y
Y
Goldstein
M
M
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
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