Ruiz A, Sanz J M, Gonzalez-Calero G, Fernández M, Andrés A, Cubero A, Ros M
Area de Bioquímica, Facultad de C. Químicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
Biochim Biophys Acta. 1996 Jan 10;1310(1):168-74. doi: 10.1016/0167-4889(95)00152-2.
Chronic treatment of rats with R-PIA 'in vivo' desensitized adenosine A1 receptor-mediated inhibition of adenylyl cyclase in brain plasma membranes and increased basal and forskolin-stimulated adenylyl cyclase. The adenosine A1 receptor agonist CHA (cyclohexyl adenosine) inhibited forskolin-stimulated adenylyl cyclase in synaptic plasma membranes from control rats but failed to do so in membranes isolated from rats treated with R-PIA. This loss of response was accompanied with a significant decrease in both, total number of adenosine A1 receptors and steady-state level of alpha-Gi in synaptic plasma membranes. An increase in the steady-state level of alpha-Gs in synaptic plasma membranes was also observed by R-PIA treatment. Concurrently, a significant increase of adenosine A1 receptors was observed in microsomes and coated vesicles. These results demonstrate adenosine A1 receptor desensitization in rat brain by 'in vivo' treatment with R-PIA and suggest a role for coated vesicles in the internalization of G-protein coupled receptors.
用R-PIA对大鼠进行长期“体内”治疗，可使脑细胞膜中腺苷A1受体介导的腺苷酸环化酶抑制作用脱敏，并增加基础和福司可林刺激的腺苷酸环化酶活性。腺苷A1受体激动剂CHA（环己基腺苷）可抑制对照大鼠突触质膜中福司可林刺激的腺苷酸环化酶，但对用R-PIA处理的大鼠分离出的质膜则无此作用。这种反应丧失伴随着突触质膜中腺苷A1受体总数和α-Gi稳态水平的显著降低。用R-PIA处理还观察到突触质膜中α-Gs稳态水平的增加。同时，在微粒体和包被小泡中观察到腺苷A1受体显著增加。这些结果表明，用R-PIA“体内”治疗可使大鼠脑内腺苷A1受体脱敏，并提示包被小泡在G蛋白偶联受体的内化中起作用。
