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大鼠新生门静脉肌丝敏感性增加:一种潜在机制。

Increased sensitization of the myofilaments in rat neonatal portal vein: a potential mechanism.

作者信息

Bruce L, Nixon G F

机构信息

Department of Biomedical Sciences, University of Aberdeen, UK.

出版信息

Exp Physiol. 1997 Nov;82(6):985-93. doi: 10.1113/expphysiol.1997.sp004084.

DOI:10.1113/expphysiol.1997.sp004084
PMID:9413730
Abstract

The contractile regulation of neonatal smooth muscle was studied in rat neonatal portal vein. Strips of beta-escin-permeabilized portal vein from 3- to 5-day-old rats and 5- to 6-week-old rats were mounted on a 'bubble chamber' in calcium solutions buffered with 10 mM EGTA. Although the overall tension development was lower in neonatal muscle as expected, the calcium sensitivity of the neonatal permeabilized portal vein was significantly higher than in developed portal vein. Endothelin-1-induced sensitization of the myofilaments was investigated. Endothelin-1 produced an increase in tension of permeabilized neonatal portal vein in a calcium solution buffered with 10 mM EGTA. This sensitization was proportionally higher in neonatal than in developed smooth muscle, despite similar initial submaximal calcium contractions. GTP gamma S-induced calcium sensitization was also proportionally higher in neonatal permeabilized strips than in fully developed smooth muscle. These changes may be due to alterations in the intracellular signalling pathways which mediate calcium sensitization in smooth muscle. As some endothelin-1-mediated responses are known to occur via activation of the heterotrimeric GTP-binding protein, Gq, the levels of protein expression of Gq alpha were studied. In membrane preparations from neonatal rat portal vein the expression of Gq alpha was significantly higher than in portal vein membrane preparations loaded with equal protein from 5- to 6-week-old rats. In conclusion, agonist-induced sensitization of the myofilaments was higher in neonatal rat portal vein than in fully developed portal vein. This difference is the result of changes in intracellular signalling and may be partly produced by the greater expression of Gq alpha observed in neonatal portal vein.

摘要

在大鼠新生门静脉中研究了新生平滑肌的收缩调节。将3至5日龄大鼠和5至6周龄大鼠的β-七叶皂苷渗透门静脉条安装在含有10 mM乙二醇双(2-氨基乙基醚)四乙酸(EGTA)缓冲的钙溶液的“气泡室”中。尽管如预期的那样新生肌肉中的总体张力发展较低,但新生渗透门静脉的钙敏感性明显高于发育成熟的门静脉。研究了内皮素-1诱导的肌丝致敏作用。在含有10 mM EGTA缓冲的钙溶液中,内皮素-1使渗透的新生门静脉张力增加。尽管最初的次最大钙收缩相似,但这种致敏作用在新生平滑肌中比在发育成熟的平滑肌中比例更高。鸟苷-5'-三磷酸γ-硫酯(GTPγS)诱导的钙致敏作用在新生渗透条带中也比在完全发育的平滑肌中比例更高。这些变化可能是由于介导平滑肌钙致敏作用的细胞内信号通路的改变。由于已知一些内皮素-1介导的反应是通过异三聚体GTP结合蛋白Gq的激活发生的,因此研究了Gqα的蛋白表达水平。在新生大鼠门静脉的膜制剂中,Gqα的表达明显高于从5至6周龄大鼠等量蛋白质加载的门静脉膜制剂。总之,激动剂诱导的肌丝致敏作用在新生大鼠门静脉中比在完全发育的门静脉中更高。这种差异是细胞内信号变化的结果,可能部分是由新生门静脉中观察到的Gqα的更高表达产生的。

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