Ransnäs L, Drott C, Lundholm K, Hjalmarson A, Jacobsson B
Department of Medicine, University of Gothenburg, Sahlgrenska Hospital, Sweden.
Circ Res. 1989 May;64(5):949-56. doi: 10.1161/01.res.64.5.949.
Malnutrition, as well as malignancy, induces alterations in heart metabolism and performance. Previous studies have implicated adrenergic mechanisms as the cause. The present study was undertaken to investigate if the adenylate cyclase system in the rat heart was affected by malnutrition. Three different animal groups with malnutrition were compared with a control group: rats with acute starvation for 14-96 hours, rats with protein-calorie malnutrition for 2 weeks, and rats with tumors. Stimulation by beta-adrenergic receptors and inhibition by muscarinic receptors of adenylate cyclase activity were not altered by malnutrition. However, conditions used for in vitro adenylate cyclase determinations were, of necessity, not physiological. Neither did the number of beta-adrenergic and muscarinic receptors change. When competition-binding experiments were performed, differences comprising agonist affinity and affinity state distribution were noted among the groups. The myocardial beta-adrenergic receptors formed a reduced number of high-affinity sites in all groups as compared with the control rats. All high-affinity sites displayed a more than 10-fold increase in affinity toward isoproterenol and an impaired sensitivity to guanine nucleotides except in heart membranes derived from rats starved less than 48 hours. While the protein-calorie restricted and the tumor-bearing rats had myocardial beta-adrenergic receptors that were unresponsive to guanine nucleotides, after 48 hours of starvation the rats exhibited an attenuated guanine-nucleotide-induced affinity shift. No changes associated with malnutrition in myocardial membrane levels of the of the stimulatory guanine-nucleotide-binding protein were detected by cholera-toxin-induced ADP-ribosylation.(ABSTRACT TRUNCATED AT 250 WORDS)
营养不良以及恶性肿瘤都会引起心脏代谢和功能的改变。先前的研究认为肾上腺素能机制是其病因。本研究旨在探讨大鼠心脏中的腺苷酸环化酶系统是否受到营养不良的影响。将三个不同的营养不良动物组与一个对照组进行比较：急性饥饿14 - 96小时的大鼠、蛋白质 - 热量营养不良2周的大鼠以及患有肿瘤的大鼠。营养不良并未改变β - 肾上腺素能受体对腺苷酸环化酶活性的刺激作用以及毒蕈碱受体对其的抑制作用。然而，用于体外测定腺苷酸环化酶的条件必然是非生理性的。β - 肾上腺素能和毒蕈碱受体的数量也没有变化。在进行竞争结合实验时，各实验组之间在激动剂亲和力和亲和力状态分布方面存在差异。与对照大鼠相比，所有实验组中心肌β - 肾上腺素能受体形成的高亲和力位点数量均减少。除了饥饿时间少于48小时的大鼠的心脏膜外，所有高亲和力位点对异丙肾上腺素的亲和力增加了10倍以上，并且对鸟嘌呤核苷酸的敏感性受损。蛋白质 - 热量受限的大鼠和荷瘤大鼠的心肌β - 肾上腺素能受体对鸟嘌呤核苷酸无反应，而饥饿48小时后的大鼠则表现出鸟嘌呤核苷酸诱导的亲和力变化减弱。通过霍乱毒素诱导的ADP - 核糖基化未检测到与营养不良相关的心肌膜中刺激性鸟嘌呤核苷酸结合蛋白水平的变化。（摘要截短于250字）
