Age-related changes in guinea pig respiratory tissues: considerations for assessment of bronchodilators.

Age-related changes in guinea pig respiratory tissues: considerations for assessment of bronchodilators.
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豚鼠呼吸组织与年龄相关的变化:评估支气管扩张剂的注意事项。

DOI:
10.1016/0014-2999(85)90281-x
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发表时间:
1985
影响因子:
5
通讯作者:
Douglas,JS
Douglas,JS
中科院分区:
医学2区
文献类型:
--
作者:
Duncan,PG;Douglas,JS

文献摘要

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未成熟豚鼠的气管组织对组胺和氨基甲胆碱的敏感性明显高于成熟动物的气管组织。未成熟动物的支气管组织比成熟动物的组织对异丙肾上腺素和沙丁胺醇更敏感,而不是气管组织。在幼年动物的支气管组织中,卡巴胆碱引起的张力和沙丁胺醇引起的松弛之间的功能拮抗作用最强。当使用诱导最大张力而不是最大张力所需的组胺浓度来诱导音调时,功能拮抗并不明显。用U 0521(10μM)或氢化可的松(200μM)抑制各年龄组动物组织中儿茶酚甲基转移酶,均不影响异丙醇或沙丁胺醇对组胺收缩组织的作用和松弛程度。我们得出结论,COMT的神经外摄取和代谢不会改变组织对所研究的松弛药的敏感性。因此,异丙肾上腺素和沙丁胺醇的松弛特性与年龄相关的变化不是由于它们的摄取或代谢的差异,而是可能反映了受体水平的变化。
Tracheal tissues from immature guinea pigs were significantly more sensitive to histamine and carbachol than their counterparts from mature animals. Bronchial but not tracheal tissues from immature animals were more sensitive to isoproterenol and salbutamol than tissues from mature animals. Functional antagonism between carbachol-induced tension and salbutamol-induced relaxation was greatest in bronchial tissues from immature animals. Functional antagonism was not evident when a concentration of histamine required to induce maximal but not supramaximal tension was used to induce tone. Inhibition of catechol-o-methyl transferase (COMT) with U 0521 (10 μM) or inhibition of extraneuronal uptake with hydrocortisone (200 μM), in tissues from animals in either age group, affected neither the potency of, nor the extent of relaxation induced by, isoproternol or salbutamol in histamine-contracted tissues. We conclude that extraneuronal uptake and metabolism by COMT do not modify tissue sensitivity to the relaxants studied. Therefore age-related changes in the relaxant properties of isoproterenol and salbutamol are not due to differences in their uptake or metabolism but probably reflect changes at the receptor level.