Role of phosphodiesterase II in cross talk between cGMP and cAMP in human neuroblastoma NB-OK-1 cells.
Cyclic nucleotides levels and cyclic nucleotide phosphodiesterase (PDE) activities were measured in human neuroblastoma NB-OK-1 cells possessing atrial natriuretic peptide (ANP) receptors of the A type and pituitary adenylate cyclase activating polypeptide (PACAP)-preferring receptors. Adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) degradation were interrelated since the increase in cGMP, induced by ANP-(99-126), stimulated the hydrolysis of cAMP by PDE isoenzyme II. In intact NB-OK-1 cells, the levels of cAMP and cGMP attained in the presence of, respectively, 1 nM PACAP-(1-27) and 10 nM ANP-(99-126), and in the absence or presence of PDE inhibitors, strongly suggested that cAMP hydrolysis was mainly achieved by isoenzyme IV, and to a lesser extent by isoenzymes I, II, and III, while cGMP was degraded by isoenzymes I, II, III, and V. More than one-half of total cAMP- and cGMP-hydrolyzing activities was present in the membrane-bound fraction. Cyclic nucleotide PDE activities separated by anion-exchange chromatography showed that isoenzymes III and IV were mainly present in the membrane fraction, while isoenzymes I, II, and V were in the cytosolic fraction.
Delporte
C
C
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
Poloczek
P
P
Winand
J
J
D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002852:Chromatography, Ion Exchange; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D005092:Exonucleases / Q000502:physiology*; D006801:Humans; D009447:Neuroblastoma / Q000503:physiopathology* / Q000517:prevention & control; D010446:Peptide Fragments / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010446:Peptide Fragments; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D005092:Exonucleases; C022650:spleen exonuclease; D006152:Cyclic GMP