Internalization and desensitization of adenosine receptors.
Internalization and desensitization of adenosine receptors.
复制标题
DOI：
10.1007/s11302-007-9086-7
复制
发表时间：
2008-03
影响因子：
3.5
通讯作者：
Beukers, Margot W.
中科院分区：
文献类型：
--
作者：
Klaasse, Elisabeth C.;IJzerman, Adriaan P.;de Grip, Willem J.;Beukers, Margot W.
关键词：
到目前为止，在人类基因组中已经鉴定出800多种不同的G蛋白偶联受体（GPCR）。腺苷受体的四种亚型（A1、A2A、A2B和A3受体）属于代表最广泛靶向的药理学蛋白质类的GPCR大家族。由于腺苷受体广泛分布于全身，并参与各种生理过程和疾病，因此人们对了解不同亚型的调节方式非常感兴趣，这是设计避免或利用这种调节的治疗药物的基础。主要的GPCR调节途径涉及G蛋白偶联受体激酶（GRKs）对活化受体的磷酸化，这一过程之后是抑制蛋白的结合。这阻止受体激活下游异源三聚体G蛋白途径，但同时允许激活抑制蛋白依赖性信号传导途径。在激动剂治疗后，腺苷受体亚型受到不同的调节。例如，A1R不容易磷酸化，内化缓慢，典型的半衰期为几个小时，而A2AR和A2BR的下调速度要快得多，通常短于1小时。A3R受到更快的下调，通常是几分钟的事。激动剂暴露后A3R的快速脱敏可能在治疗上等同于受体的拮抗剂占据。本文综述了细胞系统、组织和体内研究中不同腺苷亚型的脱敏和内化过程。此外，腺苷受体脱敏的分子机制进行了讨论。
Until now, more than 800 distinct G protein-coupled receptors (GPCRs) have been identified in the human genome. The four subtypes of the adenosine receptor (A1, A2A, A2B and A3 receptor) belong to this large family of GPCRs that represent the most widely targeted pharmacological protein class. Since adenosine receptors are widespread throughout the body and involved in a variety of physiological processes and diseases, there is great interest in understanding how the different subtypes are regulated, as a basis for designing therapeutic drugs that either avoid or make use of this regulation. The major GPCR regulatory pathway involves phosphorylation of activated receptors by G protein-coupled receptor kinases (GRKs), a process that is followed by binding of arrestin proteins. This prevents receptors from activating downstream heterotrimeric G protein pathways, but at the same time allows activation of arrestin-dependent signalling pathways. Upon agonist treatment, adenosine receptor subtypes are differently regulated. For instance, the A1Rs are not (readily) phosphorylated and internalize slowly, showing a typical half-life of several hours, whereas the A2AR and A2BR undergo much faster downregulation, usually shorter than 1 h. The A3R is subject to even faster downregulation, often a matter of minutes. The fast desensitization of the A3R after agonist exposure may be therapeutically equivalent to antagonist occupancy of the receptor. This review describes the process of desensitization and internalization of the different adenosine subtypes in cell systems, tissues and in vivo studies. In addition, molecular mechanisms involved in adenosine receptor desensitization are discussed.
登录
查看更多内容
影响因子：
3.7
作者：
Escriche, M;Burgueño, J;Franco, R
通讯作者：
Franco, R
影响因子：
2.9
作者：
CASTILLOMELENDEZ, M;KRSTEW, E;JARROTT, B
通讯作者：
JARROTT, B
影响因子：
3.1
作者：
Franco, R;Ciruela, F;Lluis, C
通讯作者：
Lluis, C
影响因子：
3.6
作者：
Ferguson, G;Watterson, KR;Palmer, TM
通讯作者：
Palmer, TM
影响因子：
2.9
作者：
Ferguson, G;Watterson, KR;Palmer, TM
通讯作者：
Palmer, TM