Captopril inhibits both dopaminergic and cholinergic neurotransmission in the central nervous system.
1. The present study was performed to investigate the effects of captopril on both dopaminergic and cholinergic neurotransmission in the rat central nervous system. 2. Slices of rat striatum were prepared and prelabelled with [3H]-dopamine or [3H]-choline. Slices were continuously superfused with Krebs'-Ringer solution and electrical stimulation (1 Hz) was performed. 3. Captopril significantly inhibited stimulation-evoked [3H]-dopamine release from rat striatal slices in a concentration-dependent manner (S2/S1 ratios: control 0.835 +/- 0.018 (n = 6); 1 x 10(-5) mol/L captopril 0.597 +/- 0.035 (n = 6; P < 0.05); 5 x 10(-5) mol/L captopril 0.561 +/- 0.041 (n = 6; P < 0.05)). However, the basal release of [3H]-dopamine was not affected by captopril. 4. Captopril also reduced stimulation-evoked [3H]-acetylcholine release in the striatum (S2/S1 ratios: control 0.891 +/- 0.016 (n = 6); 1 x 10(-5) mol/L captopril 0.794 +/- 0.011 (n = 6; P < 0.05)). 5. These results show that captopril inhibits the release of both dopamine and acetylcholine in the rat striatum. Although the mechanisms underlying the neurosuppressive effects of captopril remain to be determined, the findings suggest that the inhibition of dopaminergic and cholinergic neurotransmission may be related to the central action of the angiotensin-converting enzyme inhibitor.
Tsuda
K
K
Department of Medicine, Wakayama Medical College, Japan. tsudak@seishu.wakayama-med.ac.jp
Tsuda
S
S
Nishio
I
I
Masuyama
Y
Y
Goldstein
M
M
D000109:Acetylcholine / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014316:Tritium
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D014316:Tritium; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D000109:Acetylcholine; D004298:Dopamine