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Differential effects of calcium channel antagonists (ω-conotoxin GVIA, nifedipine, verapamil) on the electrically-evoked release of [3H]acetylcholine from the myenteric plexus, phrenic nerve and neocortex of rats

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Summary

Electrically-evoked release of [3H]acetylcholine from autonomic neurons (myenteric plexus), motoneurons (phrenic nerve) and the central nevous system (neocortex) was investigated in the presence and absence of the calcium channel antagonists ω-conotoxin GVIA, nifedipine and verapamil, whereby the same species (rat) was used in all experiments. Release of [3H]acetylcholine was measured after incubation of the tissue with [3H]choline.

ω-Conotoxin GVIA markedly reduced (70%) the evoked release of [3H]acetylcholine from the myenteric plexus of the small intestine (IC50: 0.7 nmol/l) with a similar potency at 3 and 10 Hz stimulation. An increase in the extracellular calcium concentration attenuated the inhibitory effect of ω-conotoxin GVIA. Release of [3H]acetylcholine from the rat neocortex was also inhibited (90%) by ω-conotoxin GVIA, but the potency was 19-fold lower (IC50: 13 nmol/l). However, the release of [3H]acetylcholine from the phrenic nerve was not reduced by ω-conotoxin GVIA (100 nmol/l) at 1.8 mmol/l calcium (normal concentration), whereas ω-conotoxin GVIA inhibited evoked [3H]acetylcholine release by 47% at 0.9 mmol/l calcium. Neither nifedipine (0.1 and 1 μmol/l) nor verapamil (0.1, 1 and 10 μmol/l) modified the evoked release of [3H]acetylcholine from the myenteric plexus and the phrenic nerve.

Acetylcholine release from different neurons appears to be regulated by different types of calcium channels. N-type channels play the dominant role in regulating acetylcholine release from both the myenteric plexus and the neocortex, whereas acetylcholine release from motor nerves is regulated by calcium channel(s) not yet characterized.

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Authors and Affiliations

  1. Department of Pharmacology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500, Mainz

    D. J. Dooley & J. Werhand

  2. Gödecke Research Institute, Mooswaldallee 1-9, D-7800, Freiburg, Germany

    I. Wessler & F. Schlemmer

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  1. I. Wessler
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  2. D. J. Dooley
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  3. J. Werhand
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  4. F. Schlemmer
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Wessler, I., Dooley, D.J., Werhand, J. et al. Differential effects of calcium channel antagonists (ω-conotoxin GVIA, nifedipine, verapamil) on the electrically-evoked release of [3H]acetylcholine from the myenteric plexus, phrenic nerve and neocortex of rats. Naunyn-Schmiedeberg's Arch Pharmacol 341, 288–294 (1990). https://doi.org/10.1007/BF00180653

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  • DOI: https://doi.org/10.1007/BF00180653

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