Farrukh H M, White M, Port J D, Handwerger D, Larrabee P, Klein J, Roden R A, Skerl L, Renlund D G, Feldman A M
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
J Am Coll Cardiol. 1993 Dec;22(7):1902-8. doi: 10.1016/0735-1097(93)90777-x.
The purpose of this study was to examine beta-adrenergic receptor signal transduction in denervated, previously transplanted human ventricular myocardium.
In model systems, surgical denervation typically results in both presynaptic and postsynaptic supersensitivity in beta-adrenergic receptor pathways and alteration in G protein-mediated signal transduction.
We examined beta-adrenergic receptor signal transduction in the left and right ventricles removed from nine subjects with a previous transplant and surgical denervation 25 +/- 4 months after their first transplantation. Twenty-six hearts removed from organ donors served as control hearts.
Total beta-adrenergic receptor density and stimulation of muscle contraction in isolated right ventricular trabeculae by the nonselective agonist isoproterenol were similar in the transplant and donor groups. Beta 1-receptor density was not different in the left ventricles of the two groups but tended to be reduced (by 29%, p = 0.09) in transplant right ventricles. By contrast, beta 2-receptor density was higher in transplant left and right ventricles relative to the respective values in donor ventricles by 33% in left ventricles and 97% in right ventricles (both p < 0.05). Isoproterenol, which in particulate fractions of human heart stimulates adenylyl cyclase primarily via beta 2-receptors, produced a greater increase in cyclic adenosine monophosphate generation in membranes prepared from transplant left ventricles and right ventricles compared with donors. In contrast, guanosine 5'-[beta,gamma-imido]triphosphate, sodium fluoride and forskolin, which stimulate adenylyl cyclase through nonreceptor/G protein-sensitive mechanisms, yielded similar degrees of adenylyl cyclase stimulation in the two groups, and both pertussis toxin- and cholera toxin-catalyzed adenosine diphosphate ribosylation were not altered in transplanted left ventricles.
These data indicate that the transplanted human heart exhibits an up-regulation of functional beta 2-adrenergic receptors.
本研究旨在检测去神经支配的、先前移植的人室性心肌中的β-肾上腺素能受体信号转导。
在模型系统中，手术去神经支配通常会导致β-肾上腺素能受体途径的突触前和突触后超敏反应以及G蛋白介导的信号转导改变。
我们检测了9例曾接受过移植且在首次移植后25±4个月接受手术去神经支配的受试者的左、右心室中的β-肾上腺素能受体信号转导。从器官供体获取的26颗心脏作为对照心脏。
移植组和供体组中，总的β-肾上腺素能受体密度以及非选择性激动剂异丙肾上腺素对离体右心室小梁肌收缩的刺激作用相似。两组左心室中的β1-受体密度无差异，但移植右心室中的β1-受体密度有降低趋势（降低29%，p = 0.09）。相比之下，移植左、右心室中的β2-受体密度相对于供体心室中的相应值更高，左心室中高33%，右心室中高97%（均p < 0.05）。在人心脏微粒部分中，异丙肾上腺素主要通过β2-受体刺激腺苷酸环化酶，与供体相比，其在移植左心室和右心室制备的膜中产生的环磷酸腺苷生成增加幅度更大。相比之下，通过非受体/G蛋白敏感机制刺激腺苷酸环化酶的鸟苷5'-[β,γ-亚氨基]三磷酸、氟化钠和福斯高林在两组中产生的腺苷酸环化酶刺激程度相似，并且移植左心室中百日咳毒素和霍乱毒素催化的二磷酸腺苷核糖基化均未改变。
这些数据表明，移植的人心脏表现出功能性β2-肾上腺素能受体的上调。
