Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Portugal.
Neurobiol Aging. 2012 Dec;33(12):2869-80. doi: 10.1016/j.neurobiolaging.2012.01.008. Epub 2012 Feb 23.
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.
在婴儿大鼠中，腺苷 A(2A)受体介导的神经肌肉传递调制作用超过 A1 受体介导的神经调制作用。我们研究了衰老是否会影响这种 A(2A)/A(1)受体平衡。从（3-4 周龄）婴儿、年轻成年（12-16 周龄）、老年（36-38 周龄）和老年（80-90 周龄）雄性大鼠膈神经的单个纤维中记录诱发（EPPs）和微小终板电位（MEPPs）。非 A1/A(2A)选择性激动剂 2-氯腺苷（CADO；30 nM）和腺苷激酶抑制剂碘替比啶（ITU；10 μM）增加了婴儿、年轻成年和老年成年大鼠的 EPPs 平均幅度和量子含量，但在老年大鼠中没有增加。这种促进作用被 A(2A)受体拮抗剂 ZM241385（50 nM）阻止，被 A(2A)受体激动剂 CGS21680（10 nM）模拟。A1 受体激动剂 6-环戊基腺苷（CPA；100 nM）降低了所有年龄组的 EPPs 幅度。结论是，衰老以不同的方式影响腺苷 A1 受体和 A(2A)受体介导的神经肌肉传递的突触前调制，因此，随着年龄的增长，促进作用会减弱，而抑制作用在老年动物中保持不变。随着年龄的增长，腺苷 A(2A)受体的减少可能导致神经肌肉功能的年龄相关变化。
