Malbon C C, Berrios M, Guest S J, Hadcock J R, Morris G M, Galvin-Parton P A, Wang H Y
Department of Pharmacology, State University of New York, Stony Brook 11794-8651.
Chin J Physiol. 1991;34(1):105-20.
Many neurotransmitters, hormones, and drugs express their actions through binding to cell-surface receptors that are coupled to membrane-localized effectors via GTP-binding regulatory proteins (G-proteins). Muscarinic acetylcholine, alpha- and beta-adrenergic receptors are members of this populous class of G-protein-linked receptors. Adenylyl cyclase, phospholipase C, and ion channel activities are examples of effectors regulated via these receptors. Signal transduction via G-protein-linked receptors can be regulated at the level of the receptor, G-protein(s), and effector(s). Activation of G-protein-mediated pathway propagates the signal and leads to desensitization (short-term adaptation) and then down-regulation (long-term adaptation). How transmembrane signaling is linked to expression at the level of the gene (transcriptional control), at the level of mRNA (post-transcriptional control) and at the level of the protein (post-translational modification) remains a central question of neurobiology. Investigations at each of these potential loci for regulation have begun to reveal the molecular basis for down-regulation by agonist, up-regulation by permissive hormones (like adrenal steroids), and cross-regulation among G-protein-mediated pathways. The general topic will be discussed drawing upon recent studies of the regulation of the adrenergic receptor family (alpha- and beta-). These recent advances provide a focus for a broader understanding of the integration of information between the genome and transmembrane signaling.
许多神经递质、激素和药物通过与细胞表面受体结合来发挥作用，这些受体通过鸟苷三磷酸结合调节蛋白（G蛋白）与膜定位效应器偶联。毒蕈碱型乙酰胆碱受体、α和β肾上腺素能受体属于这类众多的G蛋白偶联受体。腺苷酸环化酶、磷脂酶C和离子通道活性是通过这些受体调节的效应器的例子。通过G蛋白偶联受体的信号转导可在受体、G蛋白和效应器水平上进行调节。G蛋白介导的信号通路激活会传播信号，并导致脱敏（短期适应），然后是下调（长期适应）。跨膜信号传导如何与基因水平（转录控制）、mRNA水平（转录后控制）和蛋白质水平（翻译后修饰）的表达相联系，仍然是神经生物学的核心问题。对这些潜在调节位点的每一项研究都已开始揭示激动剂下调、允许性激素（如肾上腺类固醇）上调以及G蛋白介导的信号通路之间交叉调节的分子基础。本文将借鉴对肾上腺素能受体家族（α和β）调节的最新研究来讨论这一主题。这些最新进展为更广泛地理解基因组与跨膜信号传导之间的信息整合提供了一个重点。
