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No involvement of nicotinic receptors in the facilitation of acetylcholine outflow in mouse cortex in the presence of neostigmine and atropine
Author(s) -
Iannazzo Lydia,
Majewski Henryk
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703512
Subject(s) - mecamylamine , nicotinic agonist , acetylcholine , neostigmine , muscarinic acetylcholine receptor , chemistry , atropine , nicotinic antagonist , muscarinic antagonist , endocrinology , stimulation , cholinergic , pharmacology , medicine , acetylcholine receptor , receptor , biology , biochemistry
The role of nicotinic and muscarinic receptors in the modulation of acetylcholine release was studied using field stimulated mouse cortex slices incubated with [ 3 H]‐choline. Both acetylcholine (100 μ M ) and the cholinesterase inhibitor neostigmine (100 μ M ) inhibited the stimulation‐induced (S‐I) outflow of radioactivity but in the presence of atropine (0.3 μ M ) an enhancement was seen, which may be indicative of facilitatory nicotinic receptors. Mecamylamine (100 μ M ) was unable to antagonize the enhancement seen in the presence of acetylcholine and atropine. The nicotinic agonist dimethylphenylpiperazinium (30 μ M ) did not facilitate S‐I outflow of radioactivity. A range of nicotinic blockers had no effect on the enhancement seen in the presence of neostigmine and atropine, nor did indomethacin, the 5HT 3 antagonist MDL 7222 nor the NMDA antagonist MK‐801. The inability to block this effect suggests that nicotinic receptors are not involved. We postulate, at least for neostigmine, that the facilitation is an artefact because of the use of [ 3 H]‐choline as a radiotracer whereby the efflux of radioactivity is enhanced because the radiolabelled acetylcholine is not metabolized to choline and therefore flows out of the tissue more readily.British Journal of Pharmacology (2000) 130 , 2008–2014; doi: 10.1038/sj.bjp.0703512