Neuromuscular transmission modulation by adenosine upon aging

NEUROBIOLOGY OF AGING

卷:33

Article

Pousinha, Paula A.^1,2  Correia, Alexandra M.^1,2,3  Sebastiao, Ana M.^1,2  Ribeiro, Joaquim A.^1,2 

[1] Univ Lisbon, Fac Med, Inst Pharmacol & Neurosci, P-1649028 Lisbon, Portugal

[2] Univ Lisbon, Unit Neurosci, Inst Mol Med, P-1649028 Lisbon, Portugal

[3] Univ Lisbon, Museu Nacl Hist Nat & Ciencia, P-1649028 Lisbon, Portugal

关键词: Aging;    Adenosine;    Adenosine receptors;    Neuromuscular junction;    Neuromuscular transmission;    EPPs and MEPPs;   

DOI  :  10.1016/j.neurobiolaging.2012.01.008

来源: Elsevier

【 摘 要 】

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 mu M) 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. (C) 2012 Elsevier Inc. All rights reserved.

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