Genetic manipulation and functional analysis of cAMP signalling in cardiac muscle: implications for a new target of pharmacotherapy.

作者: K. Iwatsubo , Y. Ishikawa , T. Tsunematsu , S. Okumura

DOI: 10.1042/BST20051337

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摘要: Adenylate cyclase is a membrane-bound enzyme that catalyses the conversion of ATP into cAMP upon activation cell-surface G-protein-coupled receptors, such as β-adrenergic and initiates cascade phosphorylation reactions within cell. Type 5 adenylate major isoform in heart well striatum brain. Mice with disrupted type 5 gene exhibited normal cardiac function under basal conditions, but decreased response to isoprenaline stimulation. When mice were subjected pressure overload stress aortic banding, they developed hypertrophy, significant reduction number apoptotic myocytes preserved function. activity was inhibited pharmacologically, by use novel P-site inhibitor enhanced selectivity for this isoform, there no changes myocyte contractility, development apoptosis induced stimulation effectively prevented. These results indicate may serve better target pharmacotherapy prevent thus failure various stresses.

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