Effects of nicardipine on the release of acetylcholine in the rat central nervous system.
Recent studies have indicated that specific dihydropyridine-sensitive Ca2+ channel binding sites are present in the brain, and that they play a crucial role in synaptic function. The present study was performed to determine the effects of nicardipine, a dihydropyridine-sensitive Ca2+ channel blocker, on the release of acetylcholine in the rat central nervous system. Striatal slices of rats which had been prelabelled with [3H]acetylcholine were superfused with Krebs-Ringer solution. The slices were stimulated with either electrical pulses (1 Hz) or an excitatory amino acid, L-glutamate, and the effects of nicardipine on the release of acetylcholine were examined. Electrical stimulation produced an increase in [3H]acetylcholine release from the striatal slices. Exposure of the slices to nicardipine significantly inhibited the stimulation-evoked [3H] acetylcholine release. An endogenous excitatory amino acid, L-glutamate, also elicited release of [3H]acetylcholine. Nicardipine significantly reduced the L-glutamate-induced release of [3H]acetylcholine, and the effect was pronounced in the presence of Mg2+. These results demonstrate that nicardipine inhibits both electrically and chemically stimulated [3H]acetylcholine release from rat striatum. The ability of nicardipine to inhibit cholinergic transmission may be related to the central effect of this Ca2+ channel blocker.
Tsuda
K
K
Neurochemistry Research Laboratories, New York University Medical Center, NY 10016.
Tsuda
S
S
Nishio
I
I
Masuyama
Y
Y
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D003864:Depression, Chemical; D004558:Electric Stimulation; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005971:Glutamates; D018698:Glutamic Acid; D009529:Nicardipine; D000109:Acetylcholine