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Effects of nicotine receptor agonists on acetylcholine release from the isolated motor nerve, small intestine and trachea of rats and guinea-pigs

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Summary

The effects of nicotine receptor agonists on the release of [3H]acetylcholine from the phrenic nerve, the small intestine and the trachea were investigated to characterize neuronal nicotine receptors within the peripheral nervous system. Contraction of the indirectly-stimulated hemidiaphragm was recorded to investigate desensitization of the postsynaptic muscular nicotine receptors. Nicotine, cytisine, 1,1-dimethyl-4-phenylpiperazinium and 2-(4-aminophenyl)-ethyl-trimethyl-ammoniumiodide caused a concentration-dependent (0.1–30 μM) increase in evoked [3H]acetylcholine release from the phrenic nerve, whereby bell-shaped concentration-response curves were obtained. The rank order of decreasing potency was: nicotine > cytisine > 1,1-dimethyl-4-phenylpiperazinium > 2-(4-aminophenyl)-ethyl-trimethyl-ammoniumiodide. The presynaptic effects of nicotine depended strongly on the exposure time: facilitation occurred after a short 20 s exposure and inhibition after a 3 min exposure, whereas nicotine no longer affected evoked [3H]acetylcholine release after a 15 min exposure. Pre-exposure (40 min) of the phrenic nerve to 0.3 μM nicotine prevented any subsequent modulatory effect of a high nicotine concentration. In contrast, the contraction of the indirectly-stimulated hemidiaphragm remained unaffected in the presence of 0.3–30 μM nicotine, but a concentration of 1 mM nicotine abolished skeletal muscle contraction. Nicotine (10 μM) produced a substantial release of [3H]acetylcholine in the small intestine but not in the isolated trachea. The present experiments show presynaptic nicotine receptors at the phrenic nerve, which, under appropriate conditions, can mediate facilitation of evoked transmitter release. These neuronal receptors appear more sensitive to desensitizing conditions than the postsynaptic muscular nicotine receptors. Nicotine also mediates a transient release of acetylcholine in the myenteric plexus but not in the trachea, and as a consequence, applied nicotine preferentially activates smooth muscle activity in the intestine.

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Abbreviations

DMPP:

1,1-dimethyl-4-phenylpiperazinium

PAPETA:

2-(4-aminophenyl)-ethyl-trimethylammoniumiodiderine of [3H]acetylcholine release

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Germany

    I. Wessler, C. Apel, M. Garmsen & A. Klein

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  1. I. Wessler
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  2. C. Apel
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  3. M. Garmsen
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  4. A. Klein
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Wessler, I., Apel, C., Garmsen, M. et al. Effects of nicotine receptor agonists on acetylcholine release from the isolated motor nerve, small intestine and trachea of rats and guinea-pigs. Clin Investig 70, 182–189 (1992). https://doi.org/10.1007/BF00184649

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  • DOI: https://doi.org/10.1007/BF00184649

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