Increased relaxation of immature airways to β2-adrenoceptor agonists is related to attenuated expression of postjunctional smooth muscle muscarinic M2 receptors
Increased relaxation of immature airways to β2-adrenoceptor agonists is related to attenuated expression of postjunctional smooth muscle muscarinic M2 receptors
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DOI：
10.1152/japplphysiol.00948.2004
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发表时间：
2005-04-01
影响因子：
3.3
通讯作者：
Marthan, R
中科院分区：
文献类型：
--
作者：
Fayon, M;De La Roque, ED;Marthan, R
自发或激动剂诱导的气道平滑肌收缩可以在胎儿生命的早期观察到，从而解释了极低出生体重婴儿在出生后几天内可能发生支气管痉挛的原因。为了更好地控制这种支气管痉挛，本研究的目的是使用功能和分子技术的组合来研究气道平滑肌松弛对β 2受体激动剂和毒蕈碱拮抗剂的年龄特异性改变。在大鼠中，在气管中检测了β 2受体激动剂沙丁胺醇的等长舒张;我们还通过免疫化学、蛋白质印迹和实时PCR检测了气道平滑肌中的毒蕈碱受体表达（M2 R和M3 R mRNA水平）。与成年人相比，沙丁胺醇诱导的松弛是两倍更大的未成年大鼠离体气管预缩卡巴胆碱。这种效应与未成熟动物平滑肌中M2 R的较低表达相关（分别通过免疫化学和蛋白质印迹法评估为6倍和几乎2倍）。实时PCR数据表明，M2 R表达的变化，根据年龄发生在转录后水平。在成人气道中，有一个显着更大的功能效果M2 R阻断甲基辛四明相比，在未成年大鼠。由于人类新生儿肺组织的可用性有限，仅进行了研究的分子部分，并且我们观察到定性相似的效果，即，新生儿气道平滑肌中M2 R表达较低，尽管数量较小。我们的结论是，β（2）激动剂诱导的松弛增强未成熟的成年人相比，由于更大的连接后M2 R表达在成人气道平滑肌。这一发现可能对新生儿支气管收缩的临床管理具有重要意义。
Spontaneous or agonist-induced contraction of airway smooth muscle can be observed very early in fetal life, thus explaining the possible occurrence of bronchospasm in very low birth weight infants within the first days of life. In an attempt to better manage such bronchospasms, the aim of the present study was to investigate the age-specific modifications in airway smooth muscle relaxation to beta(2)-agonists and muscarinic antagonists using a combination of functional and molecular techniques. In the rat, isometric relaxation to the beta(2)-agonist salbutamol was examined in tracheae; we also examined muscarinic receptor expression (M2R and M3R mRNA levels) in airway smooth muscle by immunochemistry, Western blotting, and real-time PCR. Compared with adults, salbutamol-induced relaxation was twofold greater in immature rat isolated tracheae preconstricted by carbachol. This effect was associated with a lower expression of M2R in the smooth muscle of immature animals ( sixfold and almost twofold as assessed by immunochemistry and Western blotting, respectively). Real-time PCR data indicate that changes in M2R expression according to age occurred at a posttranscriptional level. In adult airways, there was a significantly greater functional efficacy of M2R blockade by methoctramine compared with that shown in immature rats. Because of the limited availability of human neonate lung tissue, only the molecular part of the study was performed, and we observed a qualitatively similar effect, i.e., a lower M2R expression in the neonatal airway smooth muscle, although this was quantitatively smaller. We conclude that beta(2)-agonist-induced relaxation is enhanced in immature compared with adult airways as a result of greater postjunctional M2R expression in adult airway smooth muscle. This finding may be of importance in the clinical management of bronchoconstriction in neonates.