Regulation of transsynaptically elicited increase of 3':5'-cyclic AMP by endogenous phosphodiesterase activator.
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.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000313:Adrenal Medulla / Q000201:enzymology / Q000648:ultrastructure; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000648:ultrastructure; D003080:Cold Temperature; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004793:Enzyme Reactivators / Q000378:metabolism*; D008566:Membranes / Q000201:enzymology; D008954:Models, Biological; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000201:enzymology / Q000378:metabolism*
D004793:Enzyme Reactivators; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases