The expression of desensitization of myocardial beta-adrenoceptor signal transduction system

β -肾上腺素能受体转导系统的生化改变是心脏衰竭或衰老时心肌对儿茶酚胺反应减弱的基础，目前尚不清楚。近年来，继第一个哺乳动物腺苷酸环化酶的克隆之后，又报道了6个全长腺苷酸环化酶异构体和2个其他腺苷酸环化酶的部分克隆。1)制备了5种不同的针对病毒腺苷酸环化酶V部分序列的多克隆抗体，抗体的平均效价在10-3左右。此外，MCT诱导的右心室肥厚和衰竭心肌膜腺苷酸环化酶western blot显示多条带。虽然我们通过这些多克隆抗体识别出110kDa的条带，但我们不能检测出严格的组织特异性。2)研究了mct诱导大鼠右心室肥厚和心力衰竭后心肌V型和VI型腺苷酸环化酶mRNA水平及其活性的变化。这些数据表明，在衰竭心室中，V型和VI型腺苷酸环化酶的稳态mRNA水平下降与腺苷酸环化酶催化亚基本身的活性受损是平行的。然而，早期心室肥大无衰竭状态下腺苷酸环化酶的催化活性可能受其他机制而非其基因表达调节。3)通过测定胎儿、新生儿、成年和成年大鼠心肌膜中腺苷酸环化酶的水平，探讨了β -肾上腺素能素-腺苷酸环化酶通路的发育调控及其稳态mRNA水平的贡献。心肌β -肾上腺素能受体转导系统活性的年龄相关变化受β -肾上腺素能受体密度和催化剂腺苷酸环化酶活性的调节。特别是，腺苷酸环化酶的VI型异构体含量的减少是随着年龄增长而降低催化活性的基础。少

Biochemical alteration in the beta-adrenoceptor transduction system, which underlie the diminishing response of the myocardium to catecholamines in failing hearts or aging heart, remains to be clarified. Recently, following the cloning of the first mammalian adenylyl cyclase, six full-length mammalian adenylyl cyclase isoforms and two partial clonings of other adenylyl cyclase have been reported.1) We produced five different polyclonal antibodies against the partial sequence of adenylyl cyclase V of VI.However, the average titer of these antibodies was about 10-3. In addition, western blots of adenylyl cyclase from myocardial membranes in monocrotaline (MCT)-induced right ventricular hypertrophy and failure showed multiple bands. Although we recognized a band of 110kDa by these polyclonal antibodies, we could not detect strict tissue specificity.2) We studied the alterations in myocardial mRNA levels of type V and VI adenylyl cyclase and its activity in rat heart with MCT-induced right … More ventricular hypertrophy and failure. These data suggested that a decrease in the steady state mRNA levels of type V and VI adenylyl cyclase paralleled with the impaired activity of the adenylyl cyclase catalytic subunit itself in the failing ventricle. However, adenylyl cyclase catalytic activity in the state of early hpertrophied ventricle without failure may be modulated by other mechanisms rather than its gene expression.3) We investigated the developmental regulation fo beta-adrenoceptor-adenylyl cyclase pathway in myocardial membranes form fetal, neonatal, adults and mature adult rats by measuring the adenylyl cyclase enzyme, and the contribution of the respective steady-state mRNA levels. The age-related changes in the activity of the myocardial beta-adrenoceptor transduction system are regulated by the density of beta-adrenergic receptors and by the activity of the catalyst adenylyl cyclase. In particular, a decrease in the content of the type VI isoform of adenylyl cyclase underlies the pattern of decreasing catalytic activity with age. Less