SIGNIFICANCE OF THE MULTIPLICITY OF ADENYLYL CYCLASE

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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.