EFFECTS OF CALCIUM-ANTAGONISTS ON DOPAMINE RELEASE IN THE CENTRAL NERVOUS SYSTEM : Possible Interactions with D_2-Autoreceptors and Guanosine Triphosphate-Binding Proteins
スポンサーリンク
概要
- 論文の詳細を見る
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 × 10^<-7gt:-1 × 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 × 10^<-7gt: M) inhibited the stimulation-evoked (^3H)dopamine release. Verapamil (1 × 10^<-6>M) significantly antagonized the capacity of the unlabelled dopamine to inhibit stimulation-induced (^3H)dopamine release. The blockade of D_2-receptors by a preferential D_2-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 triphosphatebinding 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) in-creased dopamine release in rat striatum, at least partially via interactions with the D_2-dopamine autoreceptors and the pertussis toxin-sensitive guanosine triphosphatebinding proteins. Furthermore, a close interaction between verap-amil and the dopamine receptors might partially explain the central effects of verapamil.
- 社団法人日本循環器学会の論文
- 1992-03-20
著者
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Masuyama Yoshiaki
Division of Cardiology, Department of Medicine. Wakayama Medical College, Japan
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Tsuda Kazushi
Department Of Cardiovascular Medicine
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Tsuda Kazushi
Neurochemistry Research Unit New York University Medical Center School Of Medicine
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TSUDA SEIKO
Neurochemistry Research Laboratories New York University Medical Center
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Tsuda Seiko
Neurochemistry Reseach Laboratories New York University Medical Center
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Tsuda Kazushi
Internal Medicine Division Of Cardiovascular Medicine Wakayama Medical University
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Masuyama Yoshiaki
Division Of Cardiology Department Of Medicine Wakayama Medical College
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