Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase

The present review focuses on the potential physiological regulations invol ving different isoforms of adenylyl cyclase (AC), the enzymatic activity re sponsible for the synthesis of cAMP from ATP. Depending on the properties a nd the relative level of the isoforms expressed in a tissue or a cell type at a specific time, extracellular signals received by the G protein-coupled receptors can be differently integrated. We report here on various aspects of such regulations, emphasizing the role of Ca2+/calmodulin in activating AC1 and AC8 in the central nervous system, the potential inhibitory effect of Ca2+ on AC5 and AC6, and the changes in the expression pattern of the i soforms during development. A particular emphasis is given to the role of c AMP during drug dependence. Present experimental limitations are also under lined (pitfalls in the interpretation of cellular transfection, scarcity of the invalidation models, and so on).