Regulation and role of adenylyl cyclase isoforms

At least nine closely related isoforms of adenylyl cyclases (ACs), the enzy mes responsible for the synthesis of cyclic AMP (cAMP) from ATP, have been cloned and characterized in mammals. Depending on the properties and the re lative levels of the isoforms expressed in a tissue or a cell type at a spe cific time, extracellular signals received through the G-protein-coupled re ceptors can be differentially integrated. The present review deals with var ious aspects of such regulations, emphasizing the role of calcium/calmoduli n in activating AC1 and AC8 in the central nervous system, the potential in hibitory effect of calcium on AC5 and AC6, and the changes in the expressio n pattern of the isoforms during development. A particular emphasis is give n to the role of cAMP during drug and ethanol dependency and to some experi mental limitations (pitfalls in the interpretation of cellular transfection , scarcity of the invalidation models, existence of complex macromolecular structures, etc).