Thomas T, St Lambert J H, Dashwood M R, Spyer K M
Autonomic Neuroscience Institute, Royal Free and University College Medical School, Royal Free Campus, London, UK.
Neuroscience. 2000;95(2):513-8. doi: 10.1016/s0306-4522(99)00473-x.
In vitro autoradiography and central microinjections of a P1 adenosine A2a receptor antagonist have been employed to investigate a possible role for centrally located adenosine A2a receptors in modulation of the baroreceptor reflex. In vitro autoradiography using [125I]4-(2-[7-amino-2-[2-furyl][3,2,4]triazolol[2,3-a][1,3,5]tr iazin-5-yl-amino]ethyl)phenol ([125I]ZM241385), the high-affinity adenosine A2a receptor antagonist, revealed a heterogeneous distribution of adenosine A2a binding sites within the lower brainstem of the rat. Image analysis showed high levels of binding in rostral regions of both the nucleus tractus solitarius and the ventrolateral medulla. Intermediate levels of binding were observed in the commissural nucleus tractus solitarius and the dorsal vagal motor nucleus, with low levels of binding in caudal regions of the nucleus tractus solitarius and the ventrolateral medulla, and the hypoglossal nucleus. Unilateral microinjections of unlabelled ZM241385 into the nucleus tractus solitarius had no effect on baseline levels of arterial pressure, heart rate and phrenic nerve activity recorded in anaesthetized, artificially ventilated rats. However, microinjections of ZM241385 reduced the bradycardia evoked by stimulation of the ipsilateral aortic nerve. In contrast, ZM241385 had no effect on the depressor response or the reduction in phrenic nerve activity evoked by aortic nerve stimulation. Our results indicate that adenosine A2a binding sites are located in a number of brainstem regions involved in autonomic function, consistent with the idea that adenosine acts as a neuromodulator of a variety of cardiorespiratory reflexes. Specifically, the data support the hypothesis that adenosine A2a receptors located within the nucleus tractus solitarius are activated during baroreceptor stimulation and have an important modulatory role in the pattern of cardiovascular changes associated with this reflex.
已采用体外放射自显影术及向中枢微量注射P1腺苷A2a受体拮抗剂，以研究位于中枢的腺苷A2a受体在压力感受器反射调节中可能发挥的作用。使用高亲和力腺苷A2a受体拮抗剂[125I]4-(2-[7-氨基-2-[2-呋喃基][3,2,4]三唑并[2,3-a][1,3,5]三嗪-5-基-氨基]乙基)苯酚([125I]ZM241385)进行的体外放射自显影显示，大鼠延髓下部腺苷A2a结合位点分布不均。图像分析表明，孤束核和延髓腹外侧的嘴侧区域结合水平较高。在孤束核连合核和迷走神经背运动核中观察到中等结合水平，而在孤束核和延髓腹外侧的尾侧区域以及舌下神经核中结合水平较低。向孤束核单侧微量注射未标记的ZM241385对麻醉、人工通气大鼠记录的动脉压、心率和膈神经活动的基线水平没有影响。然而，注射ZM241385可减轻同侧主动脉神经刺激诱发的心动过缓。相比之下，ZM241385对主动脉神经刺激诱发的降压反应或膈神经活动降低没有影响。我们的结果表明，腺苷A2a结合位点位于多个参与自主功能的脑干区域，这与腺苷作为多种心肺反射的神经调节剂的观点一致。具体而言，数据支持以下假设：在压力感受器刺激期间，位于孤束核内的腺苷A2a受体被激活，并在与该反射相关的心血管变化模式中发挥重要的调节作用。
