Distribution of Cyclic Adenosine Monophosphate in Rat Brain

Ebadi, Manuchair; Weiss, Benjamin; Costa, E.

doi:10.1001/archneur.1971.00480340085009

Cited by 20 publications

(4 citation statements)

References 24 publications

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“…These changes might then prevent the expression of neuronal differentiated functions in the mutated nerve cell, causing it to become a cancer cell. For example, the adult brain has particularly high levels of adenylate cyclase and phosphodiesterase activities and also a high level of cyclic AMP (Butcher & Sutherland, 1962;Ebadi et al, 1971 ;Sutherland et al, 1962). This may account for the fact that the neuroblastoma cells obtained from a tumour differ quantitatively and qualitatively from one another with respect to expression of cellular properties.…”

Section: Abnormal Regulation Of Cyclic Amp Phosphodiesterase : a mentioning

confidence: 99%

“…In addition, the adult brain has particularly high activities of adenylate cyclase and cyclic AMP phosphodiesterase, and a high intracellular level of cyclic AMP (Butcher & Sutherland, 1962;Sutherland, Rall & Menon, 1962; Ebadi, Weiss & Costa, 1971).…”

Section: ( D ) Adenylate Cyclase Cyclic a M P And Cyclic A M P Phospmentioning

confidence: 99%

“…This finding is consistent with the observations made on the mammalian nervous system. For example, the adult brain has particularly high levels of adenylate cyclase and phosphodiesterase activities and also a high level of cyclic AMP (Butcher & Sutherland, 1962;Ebadi et al., 1971 ; Sutherland et al, 1962). Adenylate cyclase and phosphodiesterase activities increase during the development of mammalian brain (Weiss et al, 1971).…”

Section: Abnormal Regulation Of Cyclic Amp Phosphodiesterase : a mentioning

confidence: 99%

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Differentiation of Neuroblastoma Cells in Culture

1975

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Summary 1. An elevation of the intracellular level of cyclic AMP in neuroblastoma cells by prostaglandin E1 by an inhibitor of cyclic AMP phosphodiesterase, or by analogues of cyclic AMP irreversibly induces many differentiated functions which are characteristic of mature neurones. These include formation of long neurites, increase in size of soma and nucleus associated with a rise in total RNA and protein contents, increase in activities of specific neural enzymes, loss of malignancy, increase in sensitivity of adenylate cyclase to catecholamines and blockade of cells in G1‐stage of the cell cycle. 2. Other agents, including serum‐free medium, X‐irradiation, 6‐thioguanine, cytosine arabinoside, methotrexate, 5‐bromodeoxyuridine, nerve growth factor, glial extract and hypertonic medium can induce some of the differentiated functions which are induced by high intracellular cyclic AMP. 3. Morphological differentiation and differentiated biochemical functions can each be expressed in the absence of the other. 4. Many of the responses of normal embryonic nerve cells to cyclic AMP are similar to those of neuroblastoma cells. 5. A working hypothesis for the malignancy of nerve cells has been proposed. This states that an abnormal regulation of cyclic AMP phosphodiesterase activity which allows the expression of high amounts of this enzyme in neuroblastoma cells, may be one of the early lesions during a malignant transformation of nerve cells. 6. A new experimental therapeutic model for the treatment of neuroblastoma is proposed. This involves the administration of sodium butyrate followed by the injection of l‐dihydroxyphenylalanine (l‐dopa) and prostaglandin E1 in the presence of cyclic AMP phosphodiesterase inhibitor. 7. Recent studies have elucidated the control mechanisms of some differentiated functions in neuroblastoma cells. Cyclic AMP may become an important biological tool to probe the regulation and expression of many other differentiated functions in these cells. In addition to neuroblastoma cells, other neuronal culture systems are now available for investigating the problems of differentiation and maturation in nerve cells.

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Section: Abnormal Regulation Of Cyclic Amp Phosphodiesterase : a mentioning

confidence: 99%

Section: ( D ) Adenylate Cyclase Cyclic a M P And Cyclic A M P Phospmentioning

confidence: 99%

Section: Abnormal Regulation Of Cyclic Amp Phosphodiesterase : a mentioning

confidence: 99%

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Differentiation of Neuroblastoma Cells in Culture

1975

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“…Brain contains high levels of adenylate cyclases, associated with plasma membranes (Perkins, 1973;Burkard, 1975). Levels are higher in gray than in white matter and vary considerably in different areas of the brain; the overall activity being high in the cerebral cortex and cerebellum (Klainer et al, 1962;Weiss and Costa, 1968;Ebadi et al, 1971;Schmidt et al, 1971;Steiner et al, 1972;Wellmann and Schwabe, 1973). The enzyme is present in both neuronal and glial-enriched fractions from rat and rabbit brain (Palmer, 1973) and in cultured neuroblastoma and glioma cells (Chlapowski et al, 1975).…”

Section: Metabolism and Functional Character-istics Of Cyclic Nuclmentioning

confidence: 99%

The Role of Cyclic Nucleotides in the CNS

Phillis

1977

Can. j. neurol. sci.

111

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SUMMARY:On the basis of the information presented in this review, it is difficult to reach any firm decision regarding the role of cyclic AMP (or cyclic GMP) in synaptic transmission in the brain. While it is clear that cyclic nucleotide levels can be altered by the exposure of neural tissues to various neurotransmitters, it would be premature to claim that these nucleotides are, or are not, essential to the transmission process in the pre- or postsynaptic components of the synapse. In future experiments with cyclic AMP it will be necessary to consider more critically whether the extracellularly applied nucleotide merely provides a source of adenosine and is thus activating an extracellularly located adenosine receptor, or whether it is actually reaching the hypothetical sites at which it might act as a second messenger. The application of cyclic AMP by intracellular injection techniques should minimize this particular problem, although possibly at the expense of new difficulties. Prior blockade of the adenosine receptor with agents such as theophylline or adenine xylofuranoside may also assist in the categorization of responses to extracellularly applied cyclic AMP as being a result either of activation of the adenosine receptor or of some other mechanism. Ultimately, the development of highly specific inhibitors for adenylate cyclase should provide a firm basis from which to draw conclusions about the role of cyclic AMP in synaptic transmission. Similar considerations apply to the actions of cyclic GMP and the role of its synthesizing enzyme, guanylale cyclase.The use of phosphodiesterase inhibitors in studies on cyclic nucleotides must also be approached with caution. The diverse actions of many of these compounds, which include calcium mobilization and block of adenosine uptake, could account for many of the results that have been reported in the literature.

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Neuronal maturation and synaptogenesis in the rat ventrobasal complex: Alignment with developmental changes in rate and severity of axon reaction

Matthews

Narayanan

et al. 1977

J of Comparative Neurology

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Developmental alterations in the rate and severity of axon reaction are thought to be influenced by the level of neuronal maturation and synaptogenesis. As an initial step in more carefully examining this issue, two concurrent series of studies were performed using the ventrobasal complex as a model.Sprague-Dawley albino rats, ranging in age from neonate through 60 days postnatal (dpn) were subjected to unilateral aspiration lesions encompassing somato-sensory cortex. Two t o four animals were sacrificed a t various postoperative periods of from one through 40 days. The reactive ventrobasal (VB) complex was qualitatively and quantitatively analysed employing electron microscopy and the Cajal-DeCastro reduced silver technique or a hematoxylin-eosin-Orange-M MATTHEWS, C H NARAYANAN, Y NARAYANAN A N D M ST ONGE TABLE 1 Neonate 1 2 4 6 9 1 0 12 15 20 60 A,A. EM (two stage primary fixatiunl. B, EM (single \tage p n m s r y fixation1 C, 1.M ( H + E + Orange -GI D. LM (Cajal ~ DeCastro)

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Distribution of Cyclic Adenosine Monophosphate in Rat Brain

Cited by 20 publications

References 24 publications

Differentiation of Neuroblastoma Cells in Culture

Differentiation of Neuroblastoma Cells in Culture

The Role of Cyclic Nucleotides in the CNS

Neuronal maturation and synaptogenesis in the rat ventrobasal complex: Alignment with developmental changes in rate and severity of axon reaction

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