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  • 1
    ISSN: 1432-1440
    Keywords: Motor nerve ; Intestine ; Airways ; Neuronal nicotine receptors ; Muscular nicotine receptors ; Receptor desensitization ; [3H]Acetylcholine release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Isolated trachea ; Preganglionic stimulation ; Transmural stimulation ; [3H]Acetylcholine release ; [3H]Phosphorylcholine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Basal and stimulated outflow of radioactive acetylcholine, phosphorylcholine and choline from rat and guinea-pig isolated tracheae were measured by reverse phase HPLC followed by liquid-scintillation-spectrometry. Tracheae were stimulated either by an electrical field (transmural stimulation) or by a local stimulation of the innervating parasympathetic nerves (preganglionic stimulation). Epithelium was removed in most experiments, as the epithelium inhibits acetylcholine release. The basal tritium efflux (1,600 dpm/3min) from rat isolated tracheae incubated with [3H]choline consisted of 56% [3H]phosphorylcholine and 38% [3H]choline. Preganglionic stimulation (15 Hz, 1,200 pulses) caused a 2-fold increase in tritium outflow that was abolished by the removal of extracellular calcium or by the addition of tetrodotoxin. The stimulated outflow of tritium induced by preganglionic nerve stimulation was caused by an exclusive release of [3H]acetylcholine, whereas the efflux of [3H]phosphorylcholine and [3H]choline remained unaffected by this stimulation mode. Transmural stimulation of the rat or guinea-pig trachea, however, caused, in addition to the release of [3H]acetylcholine, the outflow of [3H]phosphorylcholine. Hexamethonium (300 μmol/l) or tubocurarine (100 μmol/l) inhibited (80%) the increase in tritium outflow evoked by preganglionic stimulation, but did not affect tritium outflow evoked by transmural stimulation. Oxotremorine reduced [3H]acetylcholine release evoked by both stimulation modes, but oxotremorine was less potent with transmural stimulation. Scopolamine (0.3 μmol/l) enhanced (120%) the release of [3H]acetylcholine evoked by preganglionic nerve stimulation indicating the blockade of an endogenous negative muscarinic feedback mechanism. Epithelium-dependent inhibition of [3H]acetylcholine release was evident with both preganglionic and transmural stimulation. The present experiments demonstrate the release of [3H]acetylcholine evoked from the isolated trachea by stimulation of the preganglionic trunk of the parasympathetic cholinergic nerves. Qualitative and quantitative differences were observed in comparison to transmural stimulation. Preganglionic nerve stimulation allows a selective excitation of pulmonary, parasympathetic nerve fibres, mimics the physiological excitation of intramural neurones and is not followed by the liberation of phosphorylcholine from non-neuronal cells.
    Type of Medium: Electronic Resource
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