response to persistent beta 2-adrenergic receptor signaling

These results revealed an unanticipated beneficial therapeutic effect of beta-agonists, PLN downregulation, which acts to diminish airway hyperreactivity. Agents that inhibit PLN, and thus decrease constrictive responses, may act synergistically with the bronchodilating action of beta-agonists. A number of other genes related to [Ca2+]I are also differentially regulated by beta2AR activity some of which may act to oppose, or augment, the therapeutic efficacy of chronic beta-agonists. These genes or pathways may also represent additional targets in the treatment of asthma and related obstructive lung diseases. Keywords: genetic modification To ascertain the effects of persistent beta2AR activation on gene expression, cultured airway smooth muscle cells derived from wild-type and transgenic mice overexpressing beta2AR were subjected to DNA microarray analysis本研究结果显示，β肾上腺素受体激动剂(beta-agonists)可引发受磷蛋白(PLN)下调，这是一项此前未被预见的有益治疗效应，能够削弱气道高反应性。抑制PLN、从而减轻气道收缩反应的药物，可与β肾上腺素受体激动剂的支气管扩张作用产生协同效应。另有诸多与细胞内钙离子([Ca²⁺]I)相关的基因，其表达受β2肾上腺素能受体(beta2AR)活性的差异性调控，其中部分基因可能会削弱或增强慢性β肾上腺素受体激动剂的治疗效果。这些基因或相关信号通路，亦可作为哮喘及相关阻塞性肺疾病治疗的潜在额外靶点。 关键词：基因修饰(genetic modification) 为明确持续性β2肾上腺素能受体激活对基因表达的影响，研究人员对源自野生型(wild-type)及过表达β2肾上腺素能受体的转基因小鼠(transgenic mice)的培养气道平滑肌细胞开展了DNA微阵列分析。