Specificity of the action of cAMP agonists in the induction of RI cAMP-binding protein in mouse neuroblastoma cells.
Differentiation in the mouse neuroblastoma cells is induced by cAMP and is characterized by neurite extension and increased acetylcholinesterase, cAMP-phosphodiesterase, and RI cAMP-binding activities. To gain a better understanding of the regulation of expression and the possible function of the RI cAMP-binding protein in neuroblastoma cell differentiation, we evaluate the specificity of action of cAMP analogues and agents that increased intracellular cAMP concentration in the induction of the 47,000-dalton RI protein. The amount of RI in cell extracts was quantitated by the photoactivated incorporation of 8-N3-[32P]cAMP into the 47,000-dalton RI and by ELISA and Western blot techniques. Our results showed that dibutyryl cAMP, forskolin, prostaglandin E1, 3-isobutyl-1-methyl xanthine, and papavarine gave a 2- to 4-fold increase in the RI cAMP-binding protein coincident with the expression of various morphological and biochemical differentiation phenotypes in the mouse neuroblastoma cells. However, the effects of 8-bromo-cAMP were different. 8-Bromo-cAMP effectively promoted neurite extension and increased acetylcholinesterase and cAMP-phosphodiesterase activities; however, there was no concomitant increase in the RI cAMP-binding protein. The result raises interesting questions concerning the coupling of expression of the various differentiation phenotypes in the mouse neuroblastoma cells.
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Department of Biological Sciences, Rutgers University, Piscataway, NJ 08855.
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis*; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000494:pharmacology*; D002373:Cyclic AMP Receptor Protein; D051379:Mice; D008970:Molecular Weight; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D000242:Cyclic AMP; D000527:Alprostadil