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腺苷通过受体亚型与磷脂酶C和D的差异偶联介导的独特心脏保护作用。

Distinct cardioprotective effects of adenosine mediated by differential coupling of receptor subtypes to phospholipases C and D.

作者信息

Parsons M, Young L, Lee J E, Jacobson K A, Liang B T

机构信息

Department of Medicine, Cardiovascular Division, University of Pennsylvania Medical Center, Philadelphia 19104, USA.

出版信息

FASEB J. 2000 Jul;14(10):1423-31. doi: 10.1096/fj.14.10.1423.

DOI:10.1096/fj.14.10.1423
PMID:10877835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5567777/
Abstract

Adenosine released during cardiac ischemia exerts a marked protective effect in the heart that is mediated by the A(1) and A(3) subtypes of adenosine receptors. The signaling pathways activated by these adenosine receptors have now been characterized in a chick embryo ventricular myocyte culture model of cardioprotection against ischemia. Selective A(1) and A(3) receptor agonists were shown to activate phospholipases C and D, respectively, to achieve their distinct cardioprotective effects. The specificity of the A(3) receptor-phospholipase D interaction was also demonstrated in chick embryo atrial myocytes (which do not express endogenous A(3) receptors) that had been transfected with a vector encoding the human A(3) receptor. Activation of both endogenous A(1) and A(3) receptors in ventricular myocytes resulted in a protective response greater than that induced by stimulation of either receptor alone. Agonists that activate both adenosine A(1) and A(3) receptors may thus prove beneficial for the treatment of myocardial ischemia.

摘要

心脏缺血期间释放的腺苷对心脏具有显著的保护作用，这种作用由腺苷受体的A(1)和A(3)亚型介导。目前，在针对缺血的心脏保护雏鸡胚胎心室肌细胞培养模型中，已对这些腺苷受体激活的信号通路进行了表征。选择性A(1)和A(3)受体激动剂分别被证明可激活磷脂酶C和D，以实现其独特的心脏保护作用。在已转染编码人A(3)受体载体的雏鸡胚胎心房肌细胞（不表达内源性A(3)受体）中，也证实了A(3)受体与磷脂酶D相互作用的特异性。心室肌细胞中内源性A(1)和A(3)受体的激活所产生的保护反应，大于单独刺激任一受体所诱导的反应。因此，激活腺苷A(1)和A(3)受体的激动剂可能对治疗心肌缺血有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/8a2622672aae/nihms891225f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/9906c248cde7/nihms891225f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/33a3f51d1f42/nihms891225f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/27147b4269fd/nihms891225f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/2e98a4d714ee/nihms891225f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/8a2622672aae/nihms891225f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/9906c248cde7/nihms891225f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/33a3f51d1f42/nihms891225f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/27147b4269fd/nihms891225f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/2e98a4d714ee/nihms891225f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/5567777/8a2622672aae/nihms891225f5.jpg

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