衰老的哺乳动物心脏中腺苷释放减少。

Reduced adenosine release from the aged mammalian heart.

机构信息

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA.

出版信息

J Cell Physiol. 2012 Nov;227(11):3709-14. doi: 10.1002/jcp.24079.

DOI:10.1002/jcp.24079

PMID:22378276

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3384761/

Abstract

Adenosine (ADO) released in the heart results in enhanced coronary blood flow and reduced catecholamine release and myocardial responsiveness to adrenergic stimulation (anti-adrenergic action). ADO release from the adrenergic-stimulated aged heart is less than that from the young adult heart. Because adrenergic signaling in the aged heart is impaired, this study was conducted to determine if reduced ADO release from the aged heart results from this reduced adrenergic responsiveness. Hearts of 3-4 months (young adult) and 21-22 months (aged) Fischer-344 rats were perfused with ADO deamination and re-phosphorylation inhibited. Coronary effluent ADO levels were determined. Cellular-free ADO levels with and without sodium acetate (NaAc)-induced mitochondrial AMP synthesis were assessed using formed S-adenosylhomocysteine (SAH) in L-homocysteine thiolactone (L-HC)-treated hearts. The activities of SAH-hydrolase were determined. Aged heart ADO release was 61% less than from young hearts. NaAc augmented young heart ADO release by 104%, while that of aged hearts remained unchanged. SAH synthesis was 51% and 56% lower in the aged heart in the absence and presence of NaAc, respectively, despite an 89% greater SAH hydrolase activity found in the aged hearts. Since synthesized AMP may be diverted to IMP and ultimately inosine by AMP deaminase, inosine release was determined. Aged heart inosine levels in the absence and presence of NaAc were 74% and 59% less than for the young hearts. It is concluded that a reduced mitochondrial AMP synthesis is in part responsible for the attenuation in ADO release from the adrenergic-stimulated aged heart.

摘要

腺苷（ADO）在心脏中释放会增强冠状血流量，减少儿茶酚胺的释放，并降低心肌对肾上腺素能刺激的反应性（抗肾上腺素能作用）。从受肾上腺素刺激的老年心脏中释放的 ADO 少于从年轻成年心脏中释放的 ADO。由于老年心脏中的肾上腺素能信号传导受损，因此进行了这项研究，以确定老年心脏中 ADO 释放减少是否是由于这种肾上腺素能反应性降低所致。用 ADO 脱氨酶和再磷酸化抑制物灌注 3-4 个月（年轻成年）和 21-22 个月（老年）的 Fischer-344 大鼠心脏。测定冠状流出液中的 ADO 水平。在没有和有醋酸钠（NaAc）诱导的线粒体 AMP 合成的情况下，用 L-同型半胱氨酸硫内酯（L-HC）处理的心脏中形成的 S-腺苷同型半胱氨酸（SAH）评估细胞外 ADO 水平。测定 SAH 水解酶的活性。老年心脏的 ADO 释放比年轻心脏少 61%。NaAc 使年轻心脏的 ADO 释放增加了 104%，而老年心脏的 ADO 释放则保持不变。尽管在老年心脏中发现 SAH 水解酶活性高 89%，但在没有和有 NaAc 的情况下，老年心脏中的 SAH 合成分别低 51%和 56%。由于合成的 AMP 可能被 AMP 脱氨酶转移至 IMP 并最终转移至肌苷，因此测定肌苷的释放。在没有和有 NaAc 的情况下，老年心脏的肌苷水平分别比年轻心脏低 74%和 59%。结论是，线粒体 AMP 合成减少部分导致肾上腺素刺激的老年心脏中 ADO 释放的衰减。