No involvement of nicotinic receptors in the facilitation of acetylcholine outflow in mouse cortex in the presence of neostigmine and atropine.
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 microM) and the cholinesterase inhibitor neostigmine (100 microM) inhibited the stimulation-induced (S-I) outflow of radioactivity but in the presence of atropine (0.3 microM) an enhancement was seen, which may be indicative of facilitatory nicotinic receptors. Mecamylamine (100 microM) was unable to antagonize the enhancement seen in the presence of acetylcholine and atropine. The nicotinic agonist dimethylphenylpiperazinium (30 microM) 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.
Iannazzo
L
L
Prince Henry's Institute of Medical Research, P.O. Box 5152, Clayton, Victoria, Australia 3168. lydia.iannazzo@RMIT.edu.au
Majewski
H
H
D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D018723:Bethanechol / Q000494:pharmacology; D002217:Carbachol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D009388:Neostigmine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism; D014326:Tropanes / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018721:Muscarinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D012702:Serotonin Antagonists; D014326:Tropanes; D018723:Bethanechol; D014316:Tritium; C053765:N-methylcarbamylcholine; D009388:Neostigmine; D004246:Dimethylphenylpiperazinium Iodide; D016291:Dizocilpine Maleate; D001285:Atropine; D002217:Carbachol; D002794:Choline; D000109:Acetylcholine; C042253:bemesetron