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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 325, Issue 2, pp 124–130 | Cite as

Effects of verapamil, diltiazem and ryosidine on the release of dopamine and acetylcholine in rabbit caudate nucleus slices

  • K. Starke
  • L. Späth
  • T. Wichmann
Article

Summary

Slices of the rabbit caudate nucleus were preincubated with 3H-dopamine or 3H-choline and then superfused with label-free medium. Release of 3H-dopamine and 3H-acetylcholine was elicited by either electrical stimulation at 8 (in one series 2) Hz, or an increase in the K+ concentration by 50 mmol/l, or addition of L-glutamate 1 mmol/l. Verapamil 1 μmol/l, diltiazem 1 and 10 μmol/l, and ryosidine 1 μmol/l failed to the reduce the electrically-, K+- and glutamate-evoked overflow of tritium. Verapamil 1 μmol/l and diltiazem 10 μmol/l also failed to reduce the electricallyevoked overflow (2 Hz) when dopamine receptors, neuronal dopamine uptake, and neuronal choline uptake were blocked by domperidone, nomifensine and hemicholinium, respectively. Inhibition of the evoked overflow of tritium was only obtained when concentrations were increased to verapamil 10 μmol/l, diltiazem 100 μmol/l and ryosidine 10 μmol/l. The inhibition was generally small. It was more evident for slices preincubated with 3H-choline than for those preincubated with 3H-dopamine, because in the latter verapamil, diltiazem and (much less) ryosidine accelerated the basal efflux of tritium. The inhibition of the K+-evoked overflow of tritium was probably due to blockade of Ca2+ channels because this overflow was Ca2+-dependent but tetrodotoxin-resistant. In contrast, the inhibition of the electrically- and glutamateevoked overflow possibly involved blockade of Na+ channels as well. The results indicate that three calcium antagonists from different chemical classes are very weak inhibitors of Ca2+ entry into, and hence transmitter release from, the terminal axons of central dopaminergic and cholinergic neurones. The function of the high affinity calcium antagonist binding sites that have been identified in brain remains unknown.

Key words

Neurotransmitter release Caudate nucleus Verapamil Diltiazem Ryosidine 

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Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • K. Starke
    • 1
  • L. Späth
    • 1
  • T. Wichmann
    • 1
  1. 1.Pharmakologisches InstitutUniversität FreiburgFreiburg i. Br.Federal Republic of Germany

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