Membrane physical properties determine cardiac beta-adrenergic receptor function in cirrhotic rats.
Membrane physical properties determine cardiac beta-adrenergic receptor function in cirrhotic rats.
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膜的物理特性决定肝硬化大鼠心脏β-肾上腺素能受体的功能。
DOI：
10.1152/ajpgi.1994.267.1.g87
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Sam Lee
中科院分区：
文献类型：
--
作者：
Zeng;J. Meddings;Sam Lee
为了阐明心肌病的基本膜机制，研究了心肌细胞膜的物理性质、化学组成、β-肾上腺素受体密度、结合亲和力和异丙肾上腺素刺激的环磷酸腺苷（cAMP）的产生。肝硬化是由慢性胆管结扎引起的，而对照组则进行假手术。心脏动脉硬化大鼠的质膜被发现是更刚性比对照组，主要是由于增加胆固醇磷脂比。在哮喘动物中，β-肾上腺素能功能障碍明显，β-肾上腺素受体密度降低21%，但结合亲和力无变化。尽管受体数量略有减少，β-肾上腺素受体刺激的cAMP生产减少了37%，在阿尔茨海默病大鼠。当用流化剂8-（顺式-2-正辛基环丙基）辛酸2-（2-甲氧基-乙氧基）乙酯（A2 C）孵育时，异丙肾上腺素刺激的cAMP产生也增加到与对照动物不可区分的水平。膜物理性质的恢复对β-肾上腺素受体密度或结合亲和力没有影响。这些结果表明，肝硬化时心肌细胞质膜硬度增加与β-肾上腺素能受体功能下降有关。此外，恢复正常的物理性质可能导致β-肾上腺素受体介导的收缩功能的恢复。
To elucidate the basic membrane mechanisms underlying cirrhotic cardiomyopathy, cardiac sarcolemmal plasma membrane physical properties, chemical composition, beta-adrenoceptor density, binding affinity, and isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production were studied. Cirrhosis was induced by chronic bile duct ligation, while controls underwent a sham operation. The cardiac plasma membrane of cirrhotic rats was found to be more rigid than controls, primarily due to an increased cholesterol-to-phospholipid ratio. In cirrhotic animals, beta-adrenergic dysfunction was evident with a 21% decrease in beta-adrenoceptor density but no alteration in binding affinity. Despite the modest decrease in receptor number, beta-adrenoceptor-stimulated cAMP production was decreased by 37% in cirrhotic rats. When the membrane physical properties of the cirrhotic rats were restored to normal, by incubation with the fluidizing agent 2-(2-methoxy-ethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanoate (A2C), isoproterenol-stimulated cAMP production also increased to levels indistinguishable from control animals. Restoration of membrane physical properties had no effect on either beta-adrenoceptor density or binding affinity. These results suggest that the increased rigidity of cardiomyocyte plasma membranes seen with cirrhosis is associated with decreased beta-adrenoceptor function. Moreover, restoring normal physical properties may result in restoration of beta-adrenoceptor-mediated contractile function.