Presynaptic alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate [3H]d-aspartate release from rat frontal cortex in vitro.
The presynaptic nicotinic modulation of glutamatergic transmission in the CNS has been associated with activation of the alpha7 subtype of nicotinic acetylcholine receptor (nAChR) in sub-cortical regions, whereas in the frontal cortex, non-alpha7 nAChRs have been implicated. The aim of this investigation was to directly characterise nAChR-evoked release of excitatory amino acids from rat frontal cortex, by monitoring the release of [3H]D-aspartate from superfused synaptosomes or minces. Co-administration of a nAChR agonist with a depolarising stimulus enhanced [3H]D-aspartate release above the effect of depolarising agent alone. This enhancement was blocked by the nicotinic antagonist mecamylamine. Other experiments revealed that in the absence of a depolarising stimulus, the nAChR agonists nicotine, epibatidine and anatoxin-a could evoke the release of [3H]D-aspartate in a Ca2+- and concentration-dependant manner. Differential sensitivity to the alpha7- and beta2*-selective nAChR antagonists alpha-bungarotoxin (alpha-Bgt) and dihydro-beta-erythroidine (DHbetaE) implicated two nAChR subtypes (alpha7 and beta2*), and this was supported by using the subtype-selective agonists choline (10 mM; alpha7 selective, blocked by alpha-Bgt but not by DHbetaE) and 5-Iodo-A-85380 (10 nM; beta2*-selective, blocked by DHbetaE but not by alpha-Bgt). Immunocytochemistry showed that alpha-Bgt labelling was associated with structures immunopositive for vesicular glutamate transporters, in both frontal cortex sections and synaptosome preparations, supporting the presence of alpha7 nAChR on glutamatergic terminals in rat frontal cortex.
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Stephen J
SJ
Rousseau
Ian W
IW
Jones
Ian A
IA
Pullar
Susan
S
Wonnacott
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000378:metabolism* / Q000494:pharmacology; D001384:Azetidines / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D000087522:Cyanobacteria Toxins; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D052998:Microcystins; D018613:Microscopy, Confocal / Q000379:methods; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000145:classification / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors; D014316:Tritium / Q000378:metabolism; D014326:Tropanes; D064569:alpha7 Nicotinic Acetylcholine Receptor
C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D001427:Bacterial Toxins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; C579165:Chrna7 protein, rat; D000087522:Cyanobacteria Toxins; D003998:Dicarboxylic Acids; D008387:Marine Toxins; D052998:Microcystins; D014179:Neurotransmitter Uptake Inhibitors; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011759:Pyrrolidines; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; D014326:Tropanes; D064569:alpha7 Nicotinic Acetylcholine Receptor; C120673:benzyloxyaspartate; D014316:Tritium; D001224:Aspartic Acid; D011189:Potassium Chloride; D008464:Mecamylamine; D009538:Nicotine; C509783:anatoxin a; C083486:pyrrolidine-2,4-dicarboxylic acid; D004299:Dopamine beta-Hydroxylase; D010751:Phosphopyruvate Hydratase; C082748:epibatidine; D002794:Choline; D002118:Calcium