Abstract
The modulation of [3H]ACh release by nicotinic compounds was studied in superfused rat hippocampal synaptosomes loaded with [3H]choline. (−)-Nicotine (0.1–10 μM) evoked a dose-dependent increase in [3H]ACh release; higher concentrations were less effective. Nicotine-evoked release was Ca2+-dependent, and blocked by the nicotinic antagonists dihydro-β-erythroidine, mecamylamine, and pempidine. The α7-selective antagonist methyllycaconitine did not inhibit nicotine-evoked release when tested at 1 μM, although at 10 μM some attenuation of the response was observed. Six agonists tested were equally efficacious in stimulating [3H]ACh release, as judged by the maximum responses, and gave the following EC50 values: (±)-epibatidine 0.12 μM; (+)-anatoxin-a 0.14 μM; (−)-nicotine 0.99 μM; (−)-cytisine 1.06 μM; ABT-418 2.6 μM; isoarecolone 43 μM. Each agonist generated a “bell-shaped” dose response curve, suggesting desensitisation at higher concentrations. This is supported by analysis of repetitive stimulation with (−)-nicotine and (−)-cytisine: S2/S1 ratios declined sharply with increasing concentration, whereas subsequent KCl-evoked release remained constant. These results are discussed in terms of possible nicotinic receptor subtypes that might be present on hippocampal nerve terminals.
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Abbreviations
- DHβE:
-
dihydro-β-erythroidine
- MLA:
-
methyllycaconitine
- nAChR:
-
nicotinic acetylcholine receptor
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Special issue dedicated to Dr. Herman Bachelard.
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Wilkie, G.I., Hutson, P., Sullivan, J.P. et al. Pharmacological characterization of a nicotinic autoreceptor in rat hippocampal synaptosomes. Neurochem Res 21, 1141–1148 (1996). https://doi.org/10.1007/BF02532425
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DOI: https://doi.org/10.1007/BF02532425