SIGNIFICANCE OF THE MULTIPLICITY OF ADENYLYL CYCLASE

最近的分子生物学研究已经阐明存在多种腺苷酸环化酶异构体，这些异构体在组织分布和生化性质上不同。这些研究表明，在每个组织中表达的腺苷酸环化酶的量和亚型是器官内cAMP信号的关键决定因素。特别是，心脏表达腺苷酸环化酶的两种主要亚型，称为V型和VI型。我们之前证明这些亚型主要通过儿茶酚胺受体对cAMP信号做出贡献。我们已经研究了具有多种腺苷酸环化酶亚型的意义和这种酶在细胞内的分布。我们还使用多种技术研究了这种酶的生化特性。我们还开发了一个单步，蔗糖梯度离心法，使腺苷酸环化酶容易检测。此外，我们已经开发了一个动物模型与缺陷型腺苷酸环化酶V在此期间，我们已经成功地开发了纯合子动物，这将是我们未来的研究。

Recent molecular biological studies have elucidated the presence of multiple adenylyl cyclase isoforms that are different in tissue distribution and biochemical properties. These studies have indicated that the amount and subtype of adenylyl cyclase expressed in each tissue is a key determinant of cAMP signal within the organ. In particular, the heart expresses the two major isoforms of adenylyl cyclase, named type V and VI.We previously demonstrated that these isoforms mostly contribute to the cAMP signal through catecholamine receptors. We have investigated the significance of having multiple adenylyl cyclase isoforms and the distribution of this enzyme within the cell. We have also investigated the biochemical properties of this enzyme using multiple techniques. We have also developed a single step, sucrose gradient centrifugation method that enables easy detection of adenylyl cyclase. Furthermore, we have developed an animal model with deficient adenylyl cyclase type V.During this grant period, we have successfully developed homozygous animals, which will be available to our future studies.