This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Prasad, K. N. Articles by Becker, G. Search for Related Content PubMed PubMed Citation Articles by Prasad, K. N. Articles by Becker, G.

Effect of Neurotransmitters, Guanosine Triphosphate, and Divalent Ions on the Regulation of Adenylate Cyclase Activity in Malignant and Adenosine Cyclic 3':5'-Monophosphate-induced "Differentiated" Neuroblastoma Cells¹

Department of Radiology, University of Colorado Medical Center, Denver, Colorado 80220

The effect of acetylcholine, 3,4-dihydroxyphenylethylamine, prostaglandin (PGE₁), guanosine triphosphate (GTP), and divalent ions on adenylate cyclase activity in homogenates of "differentiated" and malignant mouse neuroblastoma cells was studied. The sensitivity of adenylate cyclase to acetylcholine and 3,4-dihydroxyphenylethylamine markedly increased in adenosine cyclic 3':5'-monophosphate-induced differentiated neuroblastoma cells. Although 3,4-dihydroxyphenylethylamine stimulated adenylate cyclase activity in malignant neuroblastoma cells, it failed to do so in X-irradiation induced differentiated cells. PGE₁ and GTP stimulated adenylate cyclase activity in malignant and adenosine cyclic 3':5'-monophosphate induced differentiated neuroblastoma cells to about the same level. GTP potentiated the PGE₁ effect in differentiated cells, but it failed to do so in malignant cells. High concentrations of magnesium and manganese inhibited adenylate cyclase activity; this effect was more pronounced in differentiated cells than in malignant cells. Calcium stimulated adenylate cyclase activity in malignant and differentiated cells to about the same level. There was no significant difference in the values of K_m and V_max of adenylate cyclase activity in malignant and differentiated neuroblastoma cells. This study shows that the sensitivity of adenylate cyclase to neurotransmitters and divalent ions (magnesium and manganese) and the sensitivity of PGE₁-stimulated enzyme activity to GTP increase in adenosine cyclic 3':5'-monophosphate-induced differentiated neuroblastoma cells. Therefore, we suggest that the reverse may be true during malignant transformation of nerve cells.

¹ Supported by USPHS Grants NS-09230, and CA-12247.

Received 7/ 8/74. Accepted 10/ 1/74.