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Department of Radiology, University of Colorado Medical Center, Denver, Colorado 80220
The regulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase activity in homogenates of malignant and cyclic AMP-induced "differentiated" neuroblastoma cells was studied. Neuroblastoma cells of at least three mouse and one human clone had both the low (2 to 4 µM) and the high (66 to 106 µM) Km phosphodiesterase. In cyclic AMP-induced differentiated cells the values of Km were slightly decreased, whereas the values of Vmax appeared to be slightly increased. Magnesium and manganese stimulated phosphodiesterase activity. Calcium, zinc, copper, mercury, ethylenediaminetetraacetic acid, and imidazole completely inhibited phosphodiesterase activity in malignant cells, whereas the above agents, except ethylenediaminetetraacetic acid, only partially inhibited enzyme activity in differentiated cells. Ethylenediaminetetraacetic acid completely reduced phosphodiesterase activity in differentiated cells. The pH optimum for phosphodiesterase activity was about 8 in both malignant and differentiated cells. The present studies show that the values of Km and Vmax and the sensitivity of phosphodiesterase activity to divalent ions change in cyclic AMP-induced differentiated neuroblastoma cells, and therefore we propose that the reverse may be true during malignant transformation of nerve cells.
1 This work was supported by USPHS Grants NSO9230 and CA 12247.
Received 7/22/74. Accepted 10/ 1/74.
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