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胆碱能气道反应性与毒蕈碱受体亚型相关的年龄差异。

Age differences in cholinergic airway responsiveness in relation with muscarinic receptor subtypes.

作者信息

Lee Hye Kyung, Lim Mi Young, Bok Se-Mi, Cho Eui-Sic, Lee Eun Mi, Kim Seung Whan, Kim Young-Hoon, Kim Hae Won

机构信息

Department of Pharmacology, University of Ulsan College of Medicine, Songpagu, Seoul, South Korea.

出版信息

Life Sci. 2007 Jun 27;81(3):204-9. doi: 10.1016/j.lfs.2007.05.002. Epub 2007 May 17.

DOI:10.1016/j.lfs.2007.05.002
PMID:17568623
Abstract

Children seem more susceptible to increased airway reactivity than adults. Such an age-dependent discrepancy in airway reactivity may involve different airway smooth muscle functions. Therefore, we compared the in vivo and in vitro responsiveness of airway smooth muscles between two age groups of animals. Rats of 6 and 21 weeks old were challenged in vivo with acetylcholine (ACh) infused intravenously and airway resistance (R(aw)) was measured. Tracheal muscle was also isolated and the isometric force developed to ACh or KCl was measured. Furthermore, the level of genes encoding muscarinic receptor subtypes (M(1-3)) and acetylcholinesterase (AChE) expressed in the tracheal muscle was determined by RT-PCR. In results, the basal R(aw) was similar in the two age groups. The R(aw) at each ACh dose was significantly greater in young rats than older rats (p<0.05, n=22-27). Tracheal muscles from young rats were more sensitive to ACh than older rats (p<0.05, n=20-21), while receptor-independent muscle contraction to KCl was greater in older rats (p<0.05, n=10-19). Genes encoding AChE, M(2) and M(3) muscarinic receptors were more highly expressed in the tracheal muscles from young than older rats (p<0.05, n=4-6). In conclusion, airway smooth muscle in young rat is more sensitive to cholinergic stimulation in vivo and in vitro compared to older rats, which may be due to a higher expression of M(2) and M(3) muscarinic receptors in airway smooth muscle.

摘要

儿童似乎比成人更容易出现气道反应性增加的情况。气道反应性这种年龄依赖性差异可能涉及不同的气道平滑肌功能。因此,我们比较了两个年龄组动物气道平滑肌的体内和体外反应性。对6周龄和21周龄的大鼠进行静脉注射乙酰胆碱(ACh)的体内激发,并测量气道阻力(R(aw))。还分离出气管肌肉,测量其对ACh或KCl产生的等长力。此外,通过RT-PCR测定气管肌肉中编码毒蕈碱受体亚型(M(1 - 3))和乙酰胆碱酯酶(AChE)的基因水平。结果显示,两个年龄组的基础R(aw)相似。年轻大鼠在每个ACh剂量下的R(aw)均显著高于老年大鼠(p<0.05,n = 22 - 27)。年轻大鼠的气管肌肉对ACh比老年大鼠更敏感(p<0.05,n = 20 - 21),而老年大鼠对KCl的非受体依赖性肌肉收缩更大(p<0.05,n = 10 - 19)。与老年大鼠相比,年轻大鼠气管肌肉中编码AChE、M(2)和M(3)毒蕈碱受体的基因表达更高(p<0.05,n = 4 - 6)。总之,与老年大鼠相比,年轻大鼠的气道平滑肌在体内和体外对胆碱能刺激更敏感,这可能是由于气道平滑肌中M(2)和M(3)毒蕈碱受体的表达较高。

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