Signal transduction pathways associated with α1-adrenoceptor subtypes in cells and tissues including human prostate
Signal transduction pathways associated with α1-adrenoceptor subtypes in cells and tissues including human prostate
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DOI：
10.1159/000052317
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发表时间：
1999-01-01
期刊：
影响因子：
23.4
通讯作者：
Chapple, CR
中科院分区：
文献类型：
--
作者：
Marshall, I;Burt, RP;Chapple, CR
与α（1A）-肾上腺素受体相关的信号转导途径的复杂性越来越清楚。曾经有人认为α（1A）-亚型与细胞外Ca 2+的流入有关，而α（1B）-亚型通过肌醇磷酸盐的形成与细胞内Ca-2的释放有关。然而，α（1）-肾上腺素受体与G-蛋白的偶联导致许多不同的效应酶的激活，这些效应酶产生细胞内第二信使和生物活性的改变。多样性的一个领域是G α、β、γ异源三聚体G蛋白的多种形式，其赋予对某些效应物的特异性。在许多细胞和组织中，所有的α（1）肾上腺素受体亚型都能与磷脂酶C偶联，导致PiP（2）分解产生IP 3，释放细胞内Ca 2+，和甘油二酯，刺激蛋白激酶C。可以与α（1）-肾上腺素受体偶联的其它效应物包括磷脂酶D、腺苷酸环化酶和促分裂原活化蛋白激酶途径。后者涉及更长期的反应，并导致细胞生长增加，并且在例如前列腺以及血管平滑肌和心脏中可能是重要的。在人前列腺中，α（1）-肾上腺素受体激活导致细胞内Ca ~（2+）从对ryanodine敏感的凝视中释放，随后细胞外Ca ~（2+）内流，这一机制不同于与其他几种平滑肌中相同受体亚型相关的机制。因此，给定的α（1）亚型可能与不同系统中的各种不同的信号转导机制偶联。此外，在给定的细胞或组织中可能存在与α（1）-亚型相关的不同效应机制，例如磷脂酶C和促分裂原活化蛋白激酶。对信号转导机制复杂性的进一步理解和对特定组织中细节的阐明将为治疗干预开辟新的可能性。
The complexity of the signal transduction pathways linked to alpha(1A)-adrenoceptors are becoming clearer. At one time it was thought that the alpha(1A)-subtype was linked to the influx of extracellular Ca2+ while the alpha(1B)-subtype was linked via inosital phosphate formation to the release of intracellular Ca-2. However the coupling of the alpha(1)-adrenoceptors to G-proteins leads to the activation of a number of different effector enzymes which produce intracellular second messengers and alterations in biological activity. One area of diversity is in the many forms of the G alpha, beta, gamma heterotrimeric G-proteins which confer specificity towards certain effecters. All alpha(1)-adrenoceptor subtypes have been shown to couple to phospholipase C in many cells and tissues leading to the breakdown of PiP(2) to give IP3, which releases intraceIlular Ca2+, and diacylglycerol, which stimulates protein kinase C. Additional effecrors which can couple to alpha(1)-adrenoceptors include phosphalipase D, adenylate cyclase and the mitogen-activated protein kinase pathway. The latter involves a longer term response and causes increased cell growth and may be important in, for example, the prostate as well as in vascular smooth muscle and the heart. In human prostate alpha(1)-adrenaceptor activation leads to the release of intracellular Ca2+ from ryanodine-sensitive stare followed by an influx of extracelIular Ca2+, a mechanism different from that linked to the same receptor subtype in several other smooth muscles. Therefore a given alpha(1)-subtype may be coupled to a variety of different signal transduction mechanisms in different systems. Further, there may be different effector mechanisms linked to alpha(1)-subtypes in a given cell or tissue e.g. phospholipase C and mitogen-activated protein kinase. An increased understanding of the complexity of signal transduction mechanisms and the elucidation of the details in a particular tissue will open up new possibilities for therapeutic interventions.