Article date: August 2000
By: Lydia Iannazzo, Henryk Majewski in Volume 130, Issue 8, pages 2008-2014
The role of nicotinic and muscarinic receptors in the modulation of acetylcholine release was studied using field stimulated mouse cortex slices incubated with [3H]‐choline.
Both acetylcholine (100 μM) and the cholinesterase inhibitor neostigmine (100 μM) inhibited the stimulation‐induced (S‐I) outflow of radioactivity but in the presence of atropine (0.3 μM) an enhancement was seen, which may be indicative of facilitatory nicotinic receptors.
Mecamylamine (100 μM) was unable to antagonize the enhancement seen in the presence of acetylcholine and atropine. The nicotinic agonist dimethylphenylpiperazinium (30 μM) 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 5HT3 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 [3H]‐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.
The role of nicotinic and muscarinic receptors in the modulation of acetylcholine release was studied using field stimulated mouse cortex slices incubated with [3H]‐choline.
Both acetylcholine (100 μM) and the cholinesterase inhibitor neostigmine (100 μM) inhibited the stimulation‐induced (S‐I) outflow of radioactivity but in the presence of atropine (0.3 μM) an enhancement was seen, which may be indicative of facilitatory nicotinic receptors.
Mecamylamine (100 μM) was unable to antagonize the enhancement seen in the presence of acetylcholine and atropine. The nicotinic agonist dimethylphenylpiperazinium (30 μM) 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 5HT3 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 [3H]‐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
DOI: 10.1038/sj.bjp.0703512
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