Regulation of transsynaptically elicited increase of 3':5'-cyclic AMP by endogenous phosphodiesterase activator
| Autor: | P. Uzunov, Erminio Costa, Gnegy M |
|---|---|
| Rok vydání: | 1976 |
| Předmět: |
Biology
Models Biological chemistry.chemical_compound Adenosine Triphosphate Cytosol Enzyme Reactivators Cyclic AMP medicine Animals Cyclic adenosine monophosphate Protein kinase A Membranes Multidisciplinary Phosphoric Diester Hydrolases Kinase Activator (genetics) Brain Phosphodiesterase Rats Cold Temperature medicine.anatomical_structure chemistry Biochemistry 3' 5'-Cyclic-AMP Phosphodiesterases Adrenal Medulla Synapses Phosphorylation Adrenal medulla Protein Kinases Adenosine triphosphate Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 73:352-355 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.73.2.352 |
| Popis: | Experiments with cold exposure confirmed previous studies indicating that the endogenous protein acitvator of phosphodiesterase (PDEA) isolated by Cheung participates in the in vivo regulation of 3':5'-cyclic adenosine monophosphate (cAMP) in adrenal medulla. This activator of cAMP phosphodiesterase (PDE) (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17) is present in the particulate as well as the soluble fractions of rat brain. It was found that a purified cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37), in the presence of ATP and cAMP, stimulates 3-fold the release of PDEA from the particulate fraction of rat brain and adrenal medulla. The substrate for this phosphorylation could be either a membrane protein that binds PDEA or PDEA itself. In vivo evidence, however, obtained by injecting rats intraventricularly with [gamma-32P]ATP, indicates that the PDEA does not contain radioactive phosphate in its structure. Also, PDEA could not be phosphorylated by protein kinase in vitro. The following mechanism is postulated: when the intracellular content of cAMP increases it activates a protein kinase which phosphorylates a PDEA-binding membrane protein and releases PDEA. In turn this binds to activator-deficient high Km PDE and decreases its Km to facilitate the hydrolysis of the increased concentration of cAMP. |
| Databáze: | OpenAIRE |
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