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Hypertrophy of pheochromocytoma cells treated with nerve growth factor and activators of adenylate cyclase

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Summary

PC 12 pheochromocytoma cells treated with nerve growth factor (NGF) in combination with high concentrations of the activators of adenylate cyclase, forskolin or cholera toxin, become more neuron-like in size than cells treated with NGF or with activators of adenylate cyclase alone. Cells treated simultaneously with NGF plus forskolin or cholera toxin paradoxically show less process outgrowth than cells treated with NGF alone. Addition of forskolin or cholera toxin to cells pretreated with NGF, however, produces enlarged cells with intact processes that are indistinguishable from cultured neurons. One possible implication of these findings is that NGF might act in concert with agents that increase intracellular cyclic AMP to cause neuronal maturation during embryogenesis, and that the proper sequence of exposure to these signals is necessary for normal development. Specific activity of acetylcholinesterase is increased by NGF but is unaffected or slightly decreased by forskolin, suggesting that individual aspects of the developing neuronal phenotype are subject to different types of control.

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References

  • Bornstein MG (1958) Reconstituted rat-tail collagen used as a substrate for tissue cultures on coverslips in Maximow slides and roller tubes. Lab Invest 7:134–137

    Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Carney JA, Sizemore GW, Tyce TM (1975) Bilateral adrenal medullary hyperplasia in multiple endocrine neoplasia, type 2. Mayo Clin Proc 50:3–10

    Google Scholar 

  • Coupland RE (1965) The Natural History of the Chromaffin Cell, New York, Longmans, Green, p 47

    Google Scholar 

  • Dekker A, Oehrle JS (1971) Hyaline globules of the adrenal medulla of man. A product of lipid peroxidation? Arch Pathol 91:353

    Google Scholar 

  • DeLaTorre JC, Surgeon JW (1976) A methodological approach to rapid and sensitive monoamine histofluorescence using a modified glyoxylic acid technique. The SPG method. Histochemistry 49:81

    Google Scholar 

  • DeLellis RA, Merk FB, Warren P, Balogh K (1973) Ultrastructure and in vitro growth characteristics of a transplantable rat pheochromocytoma. Cancer 32:227–235

    Google Scholar 

  • DeLellis RA, Wolfe HJ, Gagel RF, Feldman Z, Miller HH, Gang DL, Reichlin S (1976) Adrenal medullary hyperplasia. A morphometric analysis in patients with familial medullary thyroid carcinoma. Am J Pathol 83:177–196

    Google Scholar 

  • Dichter MA, Tischler AS, Greene LA (1977) Nerve growth factor induced change in electrical excitability and acetylcholine sensitivity of a rat pheochromocytoma cell line. Nature (London) 268:501–504

    Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1:89–93

    Google Scholar 

  • Greene LA, McGuire JC (1978) Induction of ornithine decarboxylase by nerve growth factor dissociated from effects on survival and neurite outgrowth. Nature (London) 276:191–194

    Google Scholar 

  • Greene LA, Rukenstein A (1981) Regulation of acetylcholinesterase activity by nerve growth factor: Role of transcription and dissociation from effects on proliferation and neurite outgrowth. J Biol Chem 256:6363–6367

    Google Scholar 

  • Greene LA, Tischler AS (1976) Establishment of a noradrenergic clonal line or rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci USA 73:2424–2428

    Google Scholar 

  • Greene LA, Tischler AS (1982) PC 12 pheochromocytoma cultures in neurobiological research. In: Fedoroff S., Hertz L. (eds) Advances in Cellular Neurobiology. New York, Academic Press, p 373–414

    Google Scholar 

  • Greene LA, Burstein DE, McGuire JC, Black MM (1979) Cell culture studies on the mechanism of action of nerve growth factor. Soc Neurosci Symp 4:153–171

    Google Scholar 

  • Greene LA, Drexler SA, Connolly JL, Ruckenstein A, Green SH (1986) Selective inhibition of responses to nerve growth factor and of microtubule-associated protein phosphorylation by activators of adenylate cyclase. J Cell Biol 103:1967–1978

    Google Scholar 

  • Gunning PW, Landreth GE, Bothwell MA, Shooter EM (1981) Differential and synergistic actions of nerve growth factor and cyclic AMP in PC 12 cells. J Cell Biol 89:240–245

    Google Scholar 

  • Heidemann SR, Joshi HC, Schechter A, Fletcher JR, Bothwell M (1985) Synergistic effects of cyclic AMP and nerve growth factor on neurite outgrowth and microtubule stability of PC 12 cells. J Cell Biol 100:916–927

    Google Scholar 

  • Kelly RBK, Buckley M, Burgess T, Carlson SS, Caroni P, Hooper J, Katzen A, Moore HP, Pfeffer S, Schroer T (1983) Membrane traffic neurons and peptide-secreting cells. Cold Spring Harbor Symp Quant Biol 48:697–705

    Google Scholar 

  • Lee VM-Y (1986) Neuorofilament protein abnormalities in PC 12 cells: comparison with neurofilament proteins of normal cultured rat sympathetic neurons. J Neurosci 5:3039–3046

    Google Scholar 

  • Lucas CA, Czlonkowska A, Kreutzberg GW (1980) Regulation of acetylcholinesterase by nerve growth factor in the pheochromocytoma PC 12 cell line. Neurosci Lett 18:333–337

    Google Scholar 

  • Mobley WC, Schenker A, Shooter EM (1976) Characterization and isolation of proteolytically modified nerve growth factor. Biochemistry 15:5543–5551

    Google Scholar 

  • Mobtaker H, Tischler AS, Kwan PWL (1985) Hypertrophy of pheochromocytoma cells treated with nerve growth factor and activators of adenyl cyclase. Lab Invest 52:44A

    Google Scholar 

  • Ogawa M, Ishikawa T, Irimajiri A (1984) Adrenal chromaffin cells form functional cholinergic synapses in culture. Nature 397:66–68

    Google Scholar 

  • O'Lague PH, Obata K, Claude P, Furshpan EJ, Potter DD (1974) Evidence for cholinergic synapses between dissociated rat sympathetic neurons in cell culture. Proc Natl Acad Sci USA 71:3602–3606

    Google Scholar 

  • Rabe CS, Schneider JE, McGee R Jr (1982) Enhancement of depolarization-dependent neurosecretion from PC 12 cells by forskolin-induced elevation of cyclic AMP. J Cyclic Nucleotide Protein Phospor Res 8:371–384

    Google Scholar 

  • Richter-Landsberg C, Jastorff B (1986) The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC 12 cells. J Cell Biol 102:821–829

    Google Scholar 

  • Rieger F, Shelanski ML, Greene LA (1980) The effects of nerve growth factor on acetylcholinesterase and its multiple forms in cultures of rat PC 12 pheochromocytoma cells: increased total specific activity and appearance of the 16 S molecular form. Dev Biol 76:238–243

    Google Scholar 

  • Schubert D, Whitlock C (1977) Alteration of cellular adhesion by nerve growth factor. Proc Natl Acad Sci USA 9:4055–4058

    Google Scholar 

  • Seamon KB, Daly JW (1983) Forskolin, cyclic AMP and cellular physiology. Trends Pharmacol Sci 4:120–123

    Google Scholar 

  • Spector T (1983) Refinement of the Coomassie blue method of protein quantitation. Anal Biochem 86:146–156

    Google Scholar 

  • Spiegel AM, Gierschick P, Levine MA, and Downs RN (1985) Clinical implications of guanine nucleotide-binding proteins as receptor-effector couplers. New Engl J Med 312:26–33

    Google Scholar 

  • Tischler AS, Greene LA (1975) Nerve growth factor-induced process formation by cultured rat pheochromocytoma cells. Nature 258:341–342

    Google Scholar 

  • Tischler AS, Greene LA (1978) Morphological and cytochemical properties of a clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Lab Invest 39:77–89

    Google Scholar 

  • Tischler AS, Perlman RL, Nunnemacher G, Morse GM, DeLellis RA, Wolfe HJ (1982) Long term effects of dexamethasone and nerve growth factor on adrenal medullary cells cultured from young adult rats. Cell Tissue Res 225:525–542

    Google Scholar 

  • Tischler AS, DeLellis RA, Perlman RL, Allen JM, Costopoulos D, Lee YC, Nunnenmacher G, Wolfe HJ (1985a) Spontaneous proliferative lesions of the adrenal medulla in aging Long-Evans rats: Comparison to PC 12 cells, SCG cells, and human adrenal medullary hyperplasia. Lab Invest 53:486–498

    Google Scholar 

  • Tischler AS, Perlman RL, Costopoulos D, Horwitz J (1985b) Vasoactive intestinal peptide activates tyrosine hydroxylase in normal and neoplastic rat chromaffin cells in culture. Neurosci Lett 61:141–146

    Google Scholar 

  • Walicke PA, Patterson PH (1981) On the role of cyclic nucleotides in the transmitter choice made by cultured sympathetic neurons. J Neurosci 1:333–342

    Google Scholar 

  • Warren SW, Chute RW (1972) Pheochromocytoma. Cancer 29:327–331

    Google Scholar 

  • Ziegler W, Unsicker K (1981) Differential effects of cyclic AMP and cholera toxin on nerve growth factor-induced neurite outgrowth from adrenal medullary chromaffin and pheochromocytoma cells. Dev Brain Res 1:622–627

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts, USA

    Arthur S. Tischler, Hamid Mobtaker, Paul W. L. Kwan, William J. Jason, Ronald A. DeLellis & Hubert J. Wolfe

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  1. Arthur S. Tischler
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  2. Hamid Mobtaker
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  3. Paul W. L. Kwan
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  4. William J. Jason
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  5. Ronald A. DeLellis
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  6. Hubert J. Wolfe
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Tischler, A.S., Mobtaker, H., Kwan, P.W.L. et al. Hypertrophy of pheochromocytoma cells treated with nerve growth factor and activators of adenylate cyclase. Cell Tissue Res. 249, 161–169 (1987). https://doi.org/10.1007/BF00215430

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