Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release.
Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release.
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未成熟豚鼠气道平滑肌自发松弛的减少与前列腺素释放的增加有关。
DOI：
10.1152/ajplung.00401.2007
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Chitano,Pasquale
中科院分区：
文献类型：
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作者：
Wang,Lu;Pozzato,Valeria;Turato,Graziella;Madamanchi,Aasakiran;Murphy,ThomasM;Chitano,Pasquale
在刺激过程中，来自幼年豚鼠的气道平滑肌（ASM）比来自成年豚鼠的ASM具有更少的自发松弛。抑制环氧化酶（考克斯），催化前列腺素类的产生，增加这种松弛在婴儿ASM和消除年龄差异，从而表明前列腺素类减少松弛在婴儿ASM。在这项研究中，我们调查是否白三烯也参与减少自发性舒张;是否两个考克斯亚型，考克斯-1和考克斯-2，差异调节自发性舒张;以及是否前列腺素类释放是在豚鼠ASM发育调节。在不同年龄组中，我们测量了电刺激期间和之后气管条的松弛以及气管段的前列腺素释放。在不存在和存在脂氧合酶抑制剂、半胱氨酰白三烯受体-1拮抗剂、考克斯-1抑制剂或考克斯-2抑制剂的情况下研究松弛。我们发现，抑制脂氧合酶或半胱氨酰白三烯受体-1拮抗剂在任何年龄都不会增加自发性舒张，因此排除了白三烯在这种现象中的作用。抑制考克斯-2而非考克斯-1可促进自发松弛。前列腺素类的基础释放在幼年动物的组织中更丰富，并且随着年龄的增长而显著降低。血栓烷B2是所有年龄段释放的最丰富的代谢物。电刺激和上皮细胞去除不影响前列腺素释放的年龄差异。我们的结论是，增加基础前列腺素释放有助于减少自发性松弛在未成熟的豚鼠ASM与老年动物相比。通过调节ASM松弛，前列腺素类可能在年轻时的气道高反应性中发挥作用。
Airway smooth muscle (ASM) from infant guinea pigs has less spontaneous relaxation during stimulation than ASM from adults. Inhibition of cyclooxygenase (COX), which catalyzes the production of prostanoids, increases this relaxation in infant ASM and abolishes age differences, thus suggesting that prostanoids reduce relaxation in infant ASM. In this study, we investigated whether leukotrienes are also involved in reducing spontaneous relaxation; whether the two COX isoforms, COX-1 and COX-2, differentially regulate spontaneous relaxation; and whether prostanoid release is developmentally regulated in guinea pig ASM. In different age groups, we measured relaxation during and after electrical stimulation in tracheal strips as well as prostanoid release from tracheal segments. Relaxation was studied in the absence and in the presence of a lipoxygenase inhibitor, a cysteinyl leukotriene receptor-1 antagonist, a COX-1 inhibitor, or a COX-2 inhibitor. We found that inhibition of lipoxygenase or cysteinyl leukotriene receptor-1 antagonism did not increase spontaneous relaxation at any age, thus excluding a role for leukotrienes in this phenomenon. Inhibition of COX-2, but not COX-1, promoted spontaneous relaxation. The basal release of prostanoids was more abundant in tissue from infant animals and decreased significantly with age. Thromboxane B2was the most abundant metabolite released at all ages. Electrical stimulation and epithelium removal did not affect the age difference in prostanoid release. We conclude that increased basal prostanoid release contributes to the reduced spontaneous relaxation in immature guinea pig ASM compared with older animals. By regulating ASM relaxation, prostanoids may play a role in the airway hyperresponsiveness at a young age.