Summary
Nerve cell lines with stable properties are isolated from neuroblastomas, glioblastomas or pheochromocytomas by periodic cloning using defined culture media. After the action of different drugs, these cells show all morphological and biochemical signs of differentiation and maturation. Depending on the origin of the clone, the cell lines synthesise typical neurotransmitters, which are stored in vesicles. It is demonstrated on cell lines which synthesise catecholamines that noradrenergic and dopaminergic clones are particularly suitable test objects for basic research in neuropharmacology.
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Literatur
Amano T, Richelson E, Nirenberg M (1972) Neurotransmitter synthesis by neuroblastoma clones. Proc Natl Acad Sci USA 69:258–263
Angeletti RH, Bradshaw RA (1971) Nerve groth factor from mouse submaxillary gland: Amino acid sequence. Proc Natl Acad Sci USA 68:2417–2420
Augusti-Tocco G, Sato G (1969) Establishment of functional clonal lines of neurons from mouse neuroblastoma. Proc Natl Acad Sci USA 64:311–315
Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 20:415–455
Blaschko H (1939) The specific action of 1-dopa decarboxylase. J Physiol 96:50P-51P
Blaschko H (1972) Introduction. Catecholamines 1922–1971. In: Blaschko H, Muscholl E (eds) Catecholamines. Handbuch der experimentellen Pharmakologie, Bd XXXIII. Springer, Berlin Heidelberg New York, S 1–15
Bräutigam M, Dreesen R, Flosbach C-W, Herken H (1982a) Mouse neuroblastoma clone N1E-115: a suitable model for studying the action of dopamine agonists on tyrosine hydroxylase activity. Biochem Pharmacol 31:1279–1282
Bräutigam M, Dreesen R, Herken H (1982b) DOPA-release from mouse neuroblastoma clone N1E-115 into the culture medium — a test for tyrosine hydroxylase activity. Naunyn-Schmiedeberg's Arch Pharmacol 320:85–89
Bunney BS, Aghajanian GK (1975) Evidence for drug actions on both pre-and postsynaptic catecholamine receptors in the CNS. In: Usdin E, Bunney WE (eds) Pre- and postsynaptic receptors. Marcel Dekker Inc, New York, pp 89–122
Carlsson A (1959) Detection and assay of dopamine. Pharmacol Rev 11:300–304
Carlsson A (1964) Functional significance of drug-induced changes in brain monoamine levels. Progr Brain Res 8:9–27
Carlsson A (1975) Receptor-mediated control of dopamine metabolism. In: Usdin E, Bunney WE (eds) Pre- and postsynaptic receptors. Marcel Dekker Inc, New York, pp 49–65
Ciaranello RD, Hoffman HJ, Shire JGM, Axelrod J (1974) Genetic regulation of the catecholamine biosynthetic enzymes. II. Inheritance of tyrosine hydroxylase, dopamine-β-hydroxylase, and phenylethanolamine N-methyltransferase. J Biol Chem 249:4528–4536
Demis DJ, Blaschko H, Welch AD (1956) The conversion of dihydroxyphenylalanine-2-C14 (DOPA) to norepinephrine by bovine adrenal medullary homogenates. J Pharmacol Exp Ther 117:208–212
Ehringer H, Hornykiewicz O (1960) Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin Wochenschr 38:1236–1239
Euler US v (1972) Synthesis, uptake and storage of catecholamines in adrenergic nerves. The effects of drugs. In: Blaschko H, Muscholl E (eds) Catecholamines. Handbuch der experimentellen Pharmakologie, Bd. XXXIII. Springer, Berlin Heidelberg New York, S 186–230
Fedoroff S, Hertz L (eds) (1977) Cell, tissue, and organ cultures in neurobiology, Academic Press, New York San Francisco London
Felice LJ, Bruntlett CS, Shoup RE, Kissinger PT (1979) Measurements of catecholamines and their metabolites in tissue and physiological fluids using reverse-phase liquid chromatography with electrochemical detection. Proc 9th Materials Research Symposium Trace Organic Analysis, Natl Bureau of Standards Special Publication, 391–397
Felice LJ, Felice JD, Kissinger PT (1978) Determination of catecholamines in rat brain by reverse-phase ion-pair liquid chromatography. J Neurochem 31:1461–1465
Goldstein M, Freedman LS, Backstrom T (1970) The inhibition of catecholamine biosynthesis by apomorphine. J Pharm Pharmacol 22:715–717
Greene LA, Rein G (1977a) Release, storage and uptake of catecholamines by a clonal cell line of nerve growth factor (NGF) responsive pheochromocytoma cells. Brain Res 129:247–263
Greene LA, Rein G (1977b) Dopaminergic properties of a somatic cell hybrid line of mouse neuroblastoma X sympathetic ganglion cells. J Neurochem 29:141–150
Greene LA, Shooter EM (1980) The nerve growth factor: Biochemistry, synthesis, and mechanism of action. Ann Rev Neurosci 3:353–402
Greene LA, Tischler AS (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to NGF. Proc Natl Acad Sci USA 73:2424–2428
Halbhübner K, Herken H, Loos D (1978) Experimental neuropathy with Parkinson-like muscular rigidity. A suitable model for testing dopaminergic agonists and neuroleptic drugs. Arzneim-Forsch 28:1743–1752
Hamprecht B (1976) Neuronenmodelle. Angew Chem 88:211–223
Hamprecht B (1977) Structural, electrophysiological, biochemical, and pharmacological properties of neuroblastomaglioma cell hybrids in cell culture. In: Borne GH, Danielli JF (eds) International review of cytology, Bd 49. Academic Press, New York London San Francisco, pp 99–170
Harper GP, Thoenen H (1981) Target cells, biological effects, and mechanisms of action of nerve growth factor and its antibodies. Ann Rev Pharmacol Toxicol 21:205–229
Hayaishi O, Shimizu T (1980) Prostaglandin D2, neuromodulator. In: Koike M, Nagatsu T, Okuda J, Ozawa T (eds) New horizons in biological chemistry. Japan Scientific Societies Press, Tokyo, S 217–229
Helson L, Johnson GA, Smith R (1980) DOPA metabolism in neuroblastoma. Med Ped Oncol 8:317–322
Henn FA (1980) Separation of neuronal and glial cells and subcellular constituents. In: Fedoroff S, Hertz L (eds) Advances in cellular neurobiology, Bd 1. Academic Press, New York London Toronto Sydney San Francisco, pp 373–403
Herken H (1980) Neuropharmakologische Grundlagenforschung an clonalen Nervenzellinien in der Kultur. Vortrag Deutsche Akademie der Naturforscher Leopoldina Halle am 21.10.1980. Mitt Akademie Leopoldina (im Druck)
Herken H (1981) Die Verwendung adrenerger Zellinien in der neurobiologischen Forschung. Vortrag auf dem Symposium Fortschritte der Methoden — Neue Anwendungen der Deutschen Akademie der Naturforscher Leopoldina, Halle am 1.12.1981. Nova acta Leopoldina (im Druck)
Herken H, Keller K, Kolbe H, Lange K, Schneider H (1973) Experimentelle Myelopathie — Biochemische Grundlagen ihrer cellulären Pathogenese. Klin Wochenschr 51:644–657
Herken H, Meyer-Estorf G, Halbhübner K, Loos D (1976) Spastic paresis after 6-aminonicotinamide: Metabolic disorders in the spinal cord and electromyographically recorded changes in the hind limbs of rats. Naunyn-Schmiedeberg's Arch Pharmacol 293:245–255
Herrup K, Thoenen H (1979) Properties of the nerve growth factor receptor of a clonal line of rat pheochromocytoma (PC 12) cells. Exp Cell Res 121:71–78
Hoeldtke R, Kaufman S (1977) Bovine adrenal tyrosine hydroxylase. Purification and properties. J Biol Chem 252:3160–3169
Hollenbeck RA, Chuang DM, Costa F (1979) Translocation of cytosol protein kinase into nuclci and the induction of tyrosine hydroxylase in NBD-2 neuroblastoma cells. Brain Res 171:481–487
Holtz P (1939) Dopadecarboxylase. Naturwiss 27:724–727
Kebabian JW (1978) Multiple classes of dopamine receptors in mammalian central nervous system: The involvement of dopamine-sensitive adenylyl cyclase. Life Sci 23:479–484
Kehr W (1979) Über die Regulation der Dopaminsynthese und-freisetzung im Gehirn der Ratte. Habilitationsschr FB 3 Universitätsklinikum Charlottenburg, Freie Univ Berlin
Kehr W, Halbhübner K, Loos D, Herken H (1978) Impaired dopamine function and muscular rigidity induced by 6-aminonicotinamide in rats. Naunyn-Schmiedeberg's Arch Pharmacol 304:317–319
Keller K, Kolbe H, Lange K, Herken H (1972) Behaviour of the glycolytic system of rat brain and kidney in vivo after inhibition of the glucosephosphate isomerase. II. Substrate concentrations under the influence of ischemia, 6-amino-nicotinamide, and 2-deoxyglucose. Hoppe-Seyler's Z Physiol Chem 353:1389–1400
Keller K, Lange K, Noske W (1981) D-glucose transport in cultured cells of neural origin: The membrane as possible control point of glucose utilization. J Neurochem 36:1012–1017
Kissinger PT, Refshauge C, Dreiling R, Adams RN (1973) An electrochemical detector for liquid chromatography with picogram sensitivity. Anal Lett 6:465–477
Kissinger PT, Riggin RM, Alcorn RL, Rau LD (1975) Estimation of catecholamines in urine by high performance liquid chromatography with electrochemical detection. Biochem Med 13:299–306
Kolbe H, Keller K, Lange K, Herken H (1976) Metabolic consequences of drug-induced inhibition of the pentose phosphate pathway in neuroblastoma and glioma cells. Biochem Biophys Res Commun 73:378–382
Kolbe H, Keller K, Lange K, Herken H (1977) Glucose metabolism in C-1300 neuroblastoma cells after inhibition of hexose monophosphate pathway. Naunyn-Schmiedeberg's Arch Pharmacol 296:123–130
Landreth GE, Shooter EM (1980) Nerve growth factor receptors on PC 12 cells: ligand-induced conversion from low-to high-affinity states. Proc Natl Acad Sci USA 77:4751–4755
Lange K, Keller K, Herken H (1980) Glucose transport in cells of the nervous system. Neurochem Int 2:327–335
Langley JN, Dickinson WL (1889) On the local paralysis of peripheral ganglia and on the connection of different classes of nerve fibres with them. Proc Roy Soc (London) 46:423–431
Levi-Montalcini R (1966) The nerve growth factor, its mode of action on sensory and sympathetic nerve cells. Harvey Lect 60:217–259
Levi-Montalcini R (1976) The nerve growth factor: Its role in growth, differentiation and function of the sympathetic adrenergic neurons. Progr Brain Res 45:235–256
Levi-Montalcini R, Angeletti PU (1966) Immunosympathectomy. Pharmacol Rev 18:619–628
Levi-Montalcini R, Angeletti PU (1968) Nerve growth factor. Physiol Rev 48:534–569
Levitt M, Spector S, Sjoerdsma A, Udenfriend S (1965) Elucidation of the rate-limiting step in norepinephrine biosynthesis in the perfused guinea-pig heart. J Pharmacol Exp Ther 148:1–8
Loos D, Halbhübner K, Herken H (1977) Lisuride, a potent drug in the treatment of muscular rigidity in rats. Naunyn-Schmiedeberg's Arch Pharmacol 300:195–198
Loos D, Halbhübner K, Kehr W, Herken H (1979) Action of dopamine agonists on Parkinson-like muscle rigidity induced by 6-aminonicotinamide. Neurosci 4:667–676
Mandel P, Ciesielski-Treska J, Sensenbrenner M (1976) Neurons in vitro. In: Gispen WH (ed) Molecular and functional neurobiology. Elsevier, Amsterdam, pp 112–157
Markey KA, Kondo S, Shenkman L, Goldstein M (1980) Purification and characterization of tyrosine hydroxylase from a clonal phcochromocytoma cell line. Molec Pharmacol 17:79–85
Maruyama Y, Oshima T, Nakajima E (1980) Simultaneous determination of catecholamines in rat brain by reversed-phase liquid chromatography with electrochemical detection. Life Sci 26:1115–1120
Mefford IN (1981) Application of high performance liquid chromatography with electrochemical detection to neurochemical analysis: Measurement of catecholamines, serotonin and metabolites in rat brain. J Neurosci Methods 3:207–224
Minna J, Glazer D, Nirenberg M (1971) Genes for neuronal properties expressed in neuroblastoma x L cell hybrids. Proc Natl Acad Sci USA 68:234–239
Molnar I, Horvath C (1976) Reverse-phase chromatography of polar biological substances.: Separation of catechol compounds by high-performance liquid chromatography. Clin Chem 22:1497–1502
Nelson P, Ruffner W, Nirenberg M (1969) Neuronal tumor cells with excitable membranes grown in vitro. Proc Natl Acad Sci USA 64:1004–1010
Prasad KN (1975) Differentiation of neuroblastoma cells in culture. Biol Rev 50:129–165
Prasad KN (1980) Control mechanisms of malignancy and differentiation on cultures of nerve cells. In: Evans AE (ed) Advances in neuroblastoma research. Progress in cancer research and therapy, Vol 12. Raven Press, New York, pp 135–144
Ramon y Cajal S (1935) Die Neuronenlehre (Translation from the Spanish by Miskolczy D) In: Bumke O, Foerster O (Hrsg) Handbuch der Neurologie, Bd 1: Allgemeine Neurologie, I. Anatomie, Springer, Berlin, S 887–994
Sato G (Ed) (1973) Tissue culture of the nervous system. Current topics in neurobiology Vol 1, Plenum Press, New York London
Schechter AL, Bothwell MA (1981) Nerve growth factor receptors in PC 12 cells: Evidence for two receptor classes with differing cytoskeletal association. Cell 24:867–874
Schmiedeberg O (1870) Untersuchung über einige Giftwirkungen am Froschherzen. Ber Verh kgl sächs Ges Wiss Leipzig Math-Phys Klasse 22:130–141
Schubert D, Humphreys S, de Vitry F, Jacob F (1971) Induced differentiation of a neuroblastoma. Dev Biol 25:514–546
Schubert D, Jacob F (1970) 5-Bromodeoxyuridine-induced differentiation of a neuroblastoma. Proc Natl Acad Sci USA 67:247–254
Seeds NW, Gilman AG, Amano T, Nirenberg MW (1970) Regulation of axon formation by clonal lines of a neural tumor. Proc Natl Acad Sci USA 66:160–167
Sherrington CS (1906) The integrative action of the nervous system. Yale Univ Press, New Haven London
Shimizu T, Mizuno N, Amano T, Hayaishi O (1979) Prostaglandin D2, a neuromodulator. Proc Natl Acad Sci USA 76:6231–6234
Starke K (1978) Presynaptic regulation of release in the central nervous system. In: Paton DM (ed) The release of catecholamines from adrenergic neurons. Pergamon Press, Oxford New York, pp 143–183
Sugden PH, Holladay LA, Reimann EM, Corbin JD (1976) Purification and characterization of the catalytic subunit of adenosine 3′:5′-cyclic monophosphate-dependent protein kinase from bovine liver. Biochem J 159:409–422
Udenfriend S (1966) Tyrosine hydroxylase. Pharmacol Rev 18:43–51
Varon S (1977) Neural cell isolation and identification. In: Fedoroff S, Hertz L (eds) Cell, tissue, and organ cultures in neurobiology. Academic Press, New York San Francisco London, pp 237–261
Varon S, Manthorpe M (1980) Separation of neurons and glial cells by affinity methods. In: Fedoroff S, Hertz L (eds) Advances in cellular neurobiology, Vol 1. Academic Press, New York London Toronto Sydney San Francisco, pp 405–442
Vulliet PR, Langan TA, Weiner N (1980) Tyrosine hydroxylase: A substrate of cyclic AMP-dependent protein kinase. Proc Natl Acad Sci USA 77:92–96
Waymire JC, Gilmer-Waymire K (1978) Adrenergic enzymes in cultured mouse neuroblastoma: Absence of detectable aromatic-L-amino-acid decarboxylase. J Neurochem 31:693–698
Weiner N, Lee FL, Barnes E, Dreyer E (1977) In: Usdin E, Weiner N, Youdim MBH (eds) Structure and function of monoamine enzymes. Marcel Dekker Inc, New York, pp 109–148
Weiner N, Lee FL, Dreyer E, Barnes E (1978) Activation of tyrosine hydroxylase in noradrenergic neurons during acute nerve stimulation. Life Sci 22:1197–1215
Yankner BA, Shooter EM (1979) Nerve growth factor in the nucleus: interactions with receptors in the nuclear membrane. Proc Natl Acad Sci USA 76:1269–1273
Zeitz M, Lange K, Keller K, Herken H (1978) Effects of 6-aminonicotinamide on growth and acetylcholinesterase activity during differentiation of neuroblastoma cells in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 305:117–121
Zeitz M, Lange K, Keller K, Herken H (1980a) Distribution of acridine orange accumulating particles in neuroblastoma cells during differentiation and their characterization by subcellular fractionation and electron microscopy. Cell Mol Biol 25:305–314
Zeitz M, Lange K, Noske W, Keller K, Herken H (1980b) Further studies on the nature of red fluorescent structures in neuroblastoma monolayer cells vitally stained with acridine orange. Naunyn-Schmiedeberg's Arch Pharmacol 311:53–59
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Herken, H. Clonale Nervenzellinien in der Kultur — Modelle zum Studium molekularer Grundlagen neuropharmakologischer Wirkungen. Klin Wochenschr 61, 1–16 (1983). https://doi.org/10.1007/BF01484434
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DOI: https://doi.org/10.1007/BF01484434