title: Adenosine receptors and muscarinic receptors cooperate in acetylcholine release modulation in the neuromuscular synapse.
abstract: Adenosine receptors (ARs) are present in the motor terminals at the mouse neuromuscular junction. ARs and the presynaptic muscarinic acetylcholine receptors (mAChRs) share the functional control of the neuromuscular junction. We analysed their mutual interaction in transmitter release modulation. In electrophysiological experiments with unaltered synaptic transmission (muscles paralysed by blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB), we found that: (i) a collaborative action between different AR subtypes reduced synaptic depression at a moderate activity level (40 Hz); (ii) at high activity levels (100 Hz), endogenous adenosine production in the synaptic cleft was sufficient to reduce depression through A1 -type receptors (A1 Rs) and A2 A-type receptors (A2 A Rs); (iii) when the non-metabolizable 2-chloroadenosine (CADO) agonist was used, both the quantal content and depression were reduced; (iv) the protective effect of CADO on depression was mediated by A1 Rs, whereas A2 A Rs seemed to modulate A1 Rs; (v) ARs and mAChRs absolutely depended upon each other for the modulation of evoked and spontaneous acetylcholine release in basal conditions and in experimental conditions with CADO stimulation; (vi) the purinergic and muscarinic mechanisms cooperated in the control of depression by sharing a common pathway although the purinergic control was more powerful than the muscarinic control; and (vii) the imbalance of the ARs created by using subtype-selective and non-selective inhibitory and stimulatory agents uncoupled protein kinase C from evoked transmitter release. In summary, ARs (A1 Rs, A2 A Rs) and mAChRs (M1 , M2 ) cooperated in the control of activity-dependent synaptic depression and may share a common protein kinase C pathway.
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, carrer St Llorenç num 21, Reus, 43201, Spain.
authors.forename: M M
authors.initials: MM
authors.lastname: Santafe
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, carrer St Llorenç num 21, Reus, 43201, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Priego
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, carrer St Llorenç num 21, Reus, 43201, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Obis
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, carrer St Llorenç num 21, Reus, 43201, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Garcia
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, carrer St Llorenç num 21, Reus, 43201, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Tomàs
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, carrer St Llorenç num 21, Reus, 43201, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Lanuza
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, carrer St Llorenç num 21, Reus, 43201, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Tomàs
mesh_terms: D015762:2-Chloroadenosine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D020916:Conotoxins / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D058905:Purinergic Agents / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
chemical_list: D020916:Conotoxins; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D058905:Purinergic Agents; D011976:Receptors, Muscarinic; D018047:Receptors, Purinergic P1; C046101:conotoxin GIII; D015762:2-Chloroadenosine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000109:Acetylcholine
keywords: cholinergic synapses; motor nerve terminal; mouse; neuromuscular junction; neurotransmission; presynaptic receptors