Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Identification of a Na+ influx inhibitor that is significantly more potent than amiloride and devoid of the nonspecific effects of amiloride would be of great value in determining the validity of the hypothesis that mitogen-stimulated Na+ influx acts as a signal for induction of cell proliferation. In this study, we evaluated a number of amiloride analogs for potency of Na+ influx inhibition in human fibroblasts (HSWP). One analog, benzamil, was found to exhibit a 60-fold enhanced potency relative to amiloride. We also assessed the relative efficacies with which amiloride and benzamil inhibit Na+ influx and DNA synthesis in HSWP cells and neuroblastoma-glioma hybrid cells (NG108-15). Concentrations of benzamil required for 50% inhibition (ID50) of Na+ influx and DNA synthesis of HSWP cells are in excellent agreement (15 and 18 microM, respectively), an observation which, on the surface, is supportive of the hypothesis in question. Benzamil also inhibits Na+ influx of NG108-15 cells with an ID50 comparable to that for HSWP cells (18 microM) and suppresses DNA synthesis with a slightly higher ID50 (38 microM). Although the benzamil concentrations needed to inhibit cell growth and Na+ influx are in reasonable agreement, caution should be exercised in interpreting the effects of benzamil on cell growth with respect to the role of Na+ influx as we also observed that an analog of benzamil with a reduced ability to inhibit Na+ influx gave inhibition of DNA synthesis at concentrations which do not inhibit Na+ influx.
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PMID:Inhibition of Na+ influx and DNA synthesis in human fibroblasts and neuroblastoma-glioma hybrid cells by amiloride analogs. 687 50

Brain hypoxia or ischemia causes acidosis and the intracellular accumulation of Ca(2+) in neuron. The aims of the present study were to elucidate the interaction between intracellular pH and Ca(2+) during transient acidosis and its effects on the viability of neuronal and glial cells. Intracellular Ca(2+) and pH were measured using the fluorescence of fura-2 and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester in neuroblastoma (IMR-32), glioblastoma (T98G), and astrocytoma (CCF-STTG1) cell lines. The administration of 5 mM propionate caused intracellular acidification in IMR-32 and T98G cells but not in CCF-STTG1 cells. After the removal of propionate, the intracellular pH recovered to the resting level. The intracellular Ca(2+) transiently increased upon the removal of propionate in IMR-32 and T98G cells but not in CCF-STTG1 cells. The transient Ca(2+) increase caused by the withdrawal of intracellular acidification was abolished by the removal of external Ca(2+), diminished by a reduction of external Na(+), and inhibited by benzamil. Transient acidosis caused cell death, whereas the cells were more viable in the absence of external Ca(2+). Benzamil alleviated cell death caused by transient acidosis in IMR-32 and T98G cells but not in CCF-STTG1 cells. These results suggest that recovery from intracellular acidosis causes a transient increase in cytosolic Ca(2+) due to reversal of Ca(2+) transport via Na(+)/Ca(2+) exchanger coactivated with Na(+)/H(+) exchanger, which can cause cell death.
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PMID:Change in intracellular pH causes the toxic Ca2+ entry via NCX1 in neuron- and glia-derived cells. 1983 May 48