SIGNIFICANCE OF THE MULTIPLICITY OF ADENYLYL CYCLASE

最近的分子生物学研究已经阐明了多种腺酰环化酶亚型的存在，这些亚型在组织分布和生化性质上是不同的。这些研究表明，在每个组织中表达的腺酰环化酶的数量和亚型是器官内cAMP信号的关键决定因素。特别是，心脏表达腺酰环化酶的两种主要亚型，命名为V型和VI型。我们先前证明，这些亚型主要通过儿茶酚胺受体贡献cAMP信号。我们已经研究了具有多种腺酰环化酶同工酶的意义以及这种酶在细胞内的分布。我们还利用多种技术对该酶的生化性质进行了研究。我们还开发了一种单步蔗糖梯度离心法，使腺酰环化酶的检测变得容易。此外，我们还建立了V型腺酰环化酶缺陷型动物模型。在此期间，我们成功地培育了纯合子动物，这将为我们未来的研究提供参考。

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.