title: Neuromuscular transmission modulation by adenosine upon aging.
abstract: In infant rats adenosine A(2A) receptor-mediated modulation of neuromuscular transmission predominates over A1 receptor-mediated neuromodulation. We investigated whether aging affects this A(2A)/A(1) receptor balance. Evoked (EPPs) and miniature end plate potentials (MEPPs) were recorded from single fibers of (weeks-old) infant (3-4), young adult (12-16), older (36-38), and aged (80-90) male rat-diaphragm. The non A1/A(2A) selective agonist, 2-chloroadenosine (CADO; 30 nM) and the adenosine kinase inhibitor, iodotubericidin (ITU; 10 μM) increased mean amplitude and quantal content of EPPs in infant, young adult, and older adult rats, but not in aged rats. The facilitatory effects were prevented by the A(2A) receptor antagonist, ZM241385 (50 nM) and mimicked by the A(2A) receptor agonist, CGS21680 (10 nM). The A1 receptor agonist, 6-cyclopentyladenosine (CPA; 100 nM), decreased EPPs amplitude in all age groups. It is concluded that aging differently influences adenosine A1 receptor and A(2A) receptor-mediated presynaptic modulation of neuromuscular transmission, so that the facilitatory influence decreases upon aging, whereas the inhibitory influence remains unchanged in aged animals. The reduction of adenosine A(2A) receptors upon aging may contribute to the age-related changes in neuromuscular function.
authors.affiliation: Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Portugal.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Pousinha
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Correia
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sebastião
authors.forename: Joaquim A
authors.initials: JA
authors.lastname: Ribeiro
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D058914:Purinergic Antagonists / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
chemical_list: D058914:Purinergic Antagonists; D058906:Purinergic P1 Receptor Agonists; D000241:Adenosine