title: Inhibitory effects of beta-amyloid on the nicotinic receptors which stimulate glutamate release in rat hippocampus: the glial contribution.
abstract: We investigated on the neuronal nicotinic acetylcholine receptor subtypes involved in the cholinergic control of in vivo hippocampal glutamate (GLU), aspartate (ASP) and inhibitory γ-aminobutyric acid (GABA) overflow. We also investigated on the possible contribution of nicotinic acetylcholine receptors subtypes present on astrocytes in the regulation of the three neurotransmitter amino acids overflow using hippocampal gliosomes and on the effects of beta-amyloid (Aβ) 1-40 on the nicotinic control of amino acid neurotransmitter release. Nicotine was able to enhance the in vivo overflow of the three amino acids being more potent in stimulating GLU overflow. The α7 selective agonist PHA543613 induced an overflow very similar to that of nicotine. The α4β2 selective agonist 5IA85380 was significantly less potent in inducing GLU overflow while the overflow of ASP and GABA were almost inconsistent. Aβ1-40 inhibited the neurotransmitter overflow stimulated by PHA543613 but not the one evoked by 5IA85380. In hippocampal gliosomes nicotine elicited selectively GLU overflow which was also evoked by 5IA85380 and by the α7 selective agonist choline. Nicotine- and choline-induced glutamate overflow in gliosomes was inhibited by Aα1-40. In conclusion nicotine administration in vivo elicits hippocampal GLU release mostly through α7 nicotinic acetylcholine receptors likely present both on neurons and astrocytes. Aβ inhibitory effect on the nicotinic-control of GLU release seems to depend primarily to the inhibition of α7 nicotinic acetylcholine receptors functional responses.
authors.affiliation: Section of Pharmacology and Toxicology, Department of Pharmacy, University of Genoa, Genoa, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Salamone
authors.affiliation: Department of Drug Sciences, Centre of Excellence in Applied Biology, University of Pavia, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Mura
authors.affiliation: Section of Pharmacology and Toxicology, Department of Pharmacy, University of Genoa, Genoa, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Zappettini
authors.affiliation: Section of Pharmacology and Toxicology, Department of Pharmacy, University of Genoa, Genoa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Grilli
authors.affiliation: Section of Pharmacology and Toxicology, Department of Pharmacy, University of Genoa, Genoa, Italy.
authors.forename: Guendalina
authors.initials: G
authors.lastname: Olivero
authors.affiliation: Department of Drug Sciences, Centre of Excellence in Applied Biology, University of Pavia, Pavia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Preda
authors.affiliation: Department of Drug Sciences, Centre of Excellence in Applied Biology, University of Pavia, Pavia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Govoni
authors.affiliation: Section of Pharmacology and Toxicology, Department of Pharmacy, University of Genoa, Genoa, Italy; Center of Excellence for Biomedical Research, University of Genoa, Italy. Electronic address: marchi@pharmatox.unige.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Marchi
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001384:Azetidines / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D016229:Amyloid beta-Peptides; D001384:Azetidines; D019086:Bridged Bicyclo Compounds, Heterocyclic; C513163:N-(1-azabicyclo(2.2.2)oct-3-yl)furo(2,3-c)pyridine-5-carboxamide; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010446:Peptide Fragments; D011725:Pyridines; D011812:Quinuclidines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C078592:amyloid beta-protein (1-40); C403531:nicotinic receptor alpha4beta2; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D002794:Choline
keywords: Aminoacid release; Isolated nerve endings; Microdialysis; α4β2 Nicotinic receptors; α7 Nicotinic receptors; β-Amyloid