Effects of calcium-antagonists on dopamine release in the central nervous system--possible interactions with D2-autoreceptors and guanosine triphosphate-binding proteins.
The effects of calcium antagonists (verapamil and nicardipine) on central dopaminergic activity were investigated in vitro. Rat striatal slices prelabelled with (3H)dopamine and superfused with Krebs-solution were stimulated electrically at a frequency of 1 Hz. Exposure to verapamil (3.3 x 10(-7) - 1 x 10(-5) M) significantly increased both basal and stimulation-evoked (3H)dopamine release in a concentration-dependent manner. Nicardipine produced no changes in stimulation-evoked (3H)dopamine release, although a high concentration of nicardipine slightly increased basal release of (3H)dopamine. Exogenously applied unlabelled dopamine (1 x 10(-7) M) inhibited the stimulation-evoked (3H)dopamine release. Verapamil (1 x 10(-6) M) significantly antagonized the capacity of the unlabelled dopamine to inhibit stimulation-induced (3H)dopamine release. The blockade of D2-receptors by a preferential D2-antagonist, sulpiride, reduced the facilitatory effect of verapamil on stimulation-induced (3H)dopamine 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 verapamil on stimulation-induced (3H)dopamine release. The results of the present study show that verapamil (but not nicardipine) increased dopamine release in rat striatum, at least partially via interactions with the D2-dopamine autoreceptors and the pertussis toxin-sensitive guanosine triphosphate-binding proteins. Furthermore, a close interaction between verapamil and the dopamine receptors might partially explain the central effects of verapamil.
Tsuda
K
K
Neurochemistry Research Laboratories, New York University Medical Center, NY.
Tsuda
S
S
Masuyama
Y
Y
D000818:Animals; D002352:Carrier Proteins; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D019204:GTP-Binding Proteins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D002352:Carrier Proteins; D011954:Receptors, Dopamine; D013469:Sulpiride; D006160:Guanosine Triphosphate; D014700:Verapamil; D009529:Nicardipine; D019204:GTP-Binding Proteins; D004298:Dopamine