Different modulation of inhibitory and stimulatory pathways mediated by adenosine after chronic in vivo agonist exposure
Different modulation of inhibitory and stimulatory pathways mediated by adenosine after chronic in vivo agonist exposure
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DOI：
10.1016/j.brainres.2004.10.040
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发表时间：
2005-01-21
期刊：
影响因子：
2.9
通讯作者：
Martín, M
中科院分区：
文献类型：
--
作者：
Ruiz, MA;Albasanz, JL;Martín, M
用两种腺苷受体激动剂5 ′-N-乙基甲酰氨基腺苷（NECA）和R-N-6-苯基异丙腺苷（R-PIA）在大鼠脑内处理突触质膜，观察它们对突触质膜腺苷受体/腺苷酸环化酶系统的影响。NECA处理导致NECA刺激的腺苷酸环化酶活性显著丧失，表明腺苷A（2）受体介导的途径脱敏。总腺苷A（2）受体没有观察到显著差异，但G（s）蛋白水平降低，表明G（s）下调是脱敏的一种机制。另一方面，NECA处理导致高亲和力腺苷A（1）受体数量显著减少;然而，没有观察到CHA抑制的腺苷酸环化酶活性或Gi蛋白水平的变化。最后，当我们研究选择性腺苷A（1）受体激动剂R-PIA对腺苷刺激通路的影响时，发现低亲和力腺苷A（2）结合位点减少，而不影响通路的功能。这些结果表明，腺苷A（1）和A（2）受体在慢性激动剂暴露后以不同的方式调节，并表明腺苷介导的刺激和抑制途径之间存在串扰机制。(C)2004 Elsevier B. V.保留所有权利。
After 6 days of in vivo treatment with two selective adenosine receptor agonists, 5'-N-ethylcarboxamido adenosine (NECA) and R-N-6-phenylisopropiladenosine (R-PIA), we investigated their effects on adenosine receptors/adenylyl cyclase system in synaptic plasma membranes isolated from rat brain. NECA treatment caused a significant loss of NECA-stimulated adenylyl cyclase activity, suggesting a desensitization of the adenosine A(2) receptors-mediated pathway. No significant differences in total adenosine A(2) receptors were observed, but G(s) protein levels were decreased, suggesting G(s) down-regulation as a mechanism for desensitization. On the other hand, NECA treatment caused a significant decrease in high-affinity adenosine A(1) receptors population; however, no changes in CHA-inhibited adenylyl cyclase activity or Gi protein level were observed. Finally, when we studied the effects of R-PIA, a selective adenosine A(1) receptor agonist, on stimulatory pathway of adenosine, low-affinity adenosine A(2) binding sites were decreased without affecting the functionality of the pathway. These results show that adenosine A(1) and A(2) receptors are modulated in a different way after chronic agonist exposure and suggest the existence of cross-talk mechanisms between both stimulatory an inhibitory pathways mediated by adenosine. (C) 2004 Elsevier B.V. All rights reserved.