Neuromuscular transmission modulation by adenosine upon aging

Abstract In infant rats adenosine A 2A receptor-mediated modulation of neuromuscular transmission predominates over A 1 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 A 1 /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 A 1 receptor agonist, 6-cyclopentyladenosine (CPA; 100 nM), decreased EPPs amplitude in all age groups. It is concluded that aging differently influences adenosine A 1 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.