Vendite D, Sanz J M, López-Alañon D M, Vacas J, Andrés A, Ros M
Area de Bioquímica, Facultad de Químicas de la Universidad de Castilla-La Mancha, Ciudad Real, España.
Neurochem Res. 1998 Feb;23(2):211-8. doi: 10.1023/a:1022437110269.
Agonist-induced desensitization of adenosine A1 receptor-mediated inhibition of adenylyl cyclase has been studied in cerebellar granule cells. Exposure of cells to the adenosine A1 receptor agonist R-phenylisopropyl adenosine (R-PIA) from 2 to 48 h brings about desensitization of this signal transduction pathway. Associated with the desensitization process, a decrease in radioligand binding performed in intact cells with the adenosine A1 receptor agonist [3H]cyclohexyladenosine (CHA) has been detected. Simultaneously, an increase of adenosine A1 radioligand binding has also been detected in microsomes. A decrease in the steady-state level of alpha-Gi in both, plasma membrane and microsomes also has been detected during the desensitization process. These data may account for the desensitization of the inhibitory pathway of the adenylyl cyclase in cerebellar granule cells described herein. After a transient increase in adenosine A1 receptor mRNA, no changes were observed in this parameter after 12 hr of treatment with the adenosine A1 agonist R-PIA, suggesting a post-transcriptional regulation of this receptor during long-term desensitization.
已在小脑颗粒细胞中研究了激动剂诱导的腺苷A1受体介导的腺苷酸环化酶抑制作用的脱敏现象。将细胞暴露于腺苷A1受体激动剂R-苯异丙基腺苷（R-PIA）2至48小时会导致该信号转导途径脱敏。与脱敏过程相关，已检测到用腺苷A1受体激动剂[3H]环己基腺苷（CHA）在完整细胞中进行的放射性配体结合减少。同时，在微粒体中也检测到腺苷A1放射性配体结合增加。在脱敏过程中还检测到质膜和微粒体中α-Gi的稳态水平降低。本文所述的数据可能解释了小脑颗粒细胞中腺苷酸环化酶抑制途径的脱敏现象。在用腺苷A1激动剂R-PIA处理12小时后，腺苷A1受体mRNA短暂增加后，该参数未观察到变化，这表明在长期脱敏过程中该受体存在转录后调控。
