title: P2X(7) receptors exert a permissive role on the activation of release-enhancing presynaptic alpha7 nicotinic receptors co-existing on rat neocortex glutamatergic terminals.
abstract: Adenosine triphosphate (ATP) has been reported to enhance the release of glutamate by acting at P2X presynaptic receptors. Acetylcholine (ACh) can elicit glutamate release through presynaptic nicotinic cholinergic receptors (nAChRs) of the alpha7 subtype situated on glutamatergic axon terminals, provided that the terminal membrane is weakly depolarized. Considering that ATP and ACh are co-transmitters, we here investigate on the possibility that P2X and nAChRs co-exist and interact on the same glutamatergic nerve endings using purified rat neocortex synaptosomes in superfusion. ATP evoked Ca(2+)-dependent release of pre-accumulated D-[(3)H]aspartate ([(3)H]D-ASP) as well as of endogenous glutamate; (-)-nicotine, inactive on its own, potentiated the ATP-evoked release. The ATP analogue benzoylbenzoylATP (BzATP) behaved like ATP, but was approximately 30 times more potent; the potentiation of the BzATP-evoked release was blocked by methyllycaconitine or alpha-bungarotoxin. Adding inactive concentrations of (-)-nicotine, epibatidine or choline together with inactive concentrations of BzATP resulted in significant elevation of the [(3)H]D-ASP release mediated by alpha7 nAChRs. To conclude, P2X(7) receptors and alpha7 nAChRs seem to co-exist and interact on rat neocortex glutamatergic terminals; in particular, P2X(7) receptors exert a permissive role on the activation of alpha7 nAChRs, suggesting that ATP may not only evoke glutamate release on its own, but may also regulate the release of the amino acid elicited by ACh.
authors.affiliation: Department of Experimental Medicine, Pharmacology and Toxicology Section, University of Genoa, Viale Cembrano 4, 16148 Genova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Patti
authors.forename: Luca
authors.initials: L
authors.lastname: Raiteri
authors.forename: Massimo
authors.initials: M
authors.lastname: Grilli
authors.forename: Monica
authors.initials: M
authors.lastname: Parodi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Raiteri
authors.forename: Mario
authors.initials: M
authors.lastname: Marchi
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000493:pharmacokinetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004563:Electrochemistry / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D008297:Male; D019579:Neocortex / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; C546470:P2rx7 protein, rat; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D064569:alpha7 Nicotinic Acetylcholine Receptor; D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D009538:Nicotine; D000255:Adenosine Triphosphate; D008274:Magnesium; C082748:epibatidine; D002794:Choline