Τόμος 18 (2004) – Τεύχος 3 – Άρθρο 3 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Διεθνής Έκδοση – Volume 18 (2004) – Issue 3 – Article 3 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-International Edition

Title Neuropathy target esterase activity and its inhibition by phenyl saligenin phosphate and leptophos in cultured mouse N2a neuroblastoma cells
Authors M. Sachana¹, J. Flaskos², P. Glynn³ and A.J. Hargreaves

1. Department of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Liverpool, U.K.

2.  Laboratory of Biochemistry and Toxicology, Faculty of Veterinary Medicine, Aristotelian University of Thessaloniki, Thessaloniki, Greece

3. MRC Toxicology, University of Leicester, Leicester, U.K.

4. Department of Life Sciences, Nottingham Trent University, Nottingham, U.K.

Citation Sachana, M., Flaskos, J., Glynn, P., Hargreaves, A.J.: Neuropathy target esterase activity and its inhibition by phenyl saligenin phosphate and leptophos in cultured mouse N2a neuroblastoma cells, Epitheorese Klin. Farmakol. Farmakokinet. 18(3): 267-271 (2004)
Publication Date Received for publication: 30 March 2004

Accepted for publication: 15 April 2004

Full Text Language English
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Keywords Neuropathy target esterase, N2a cell, phenyl saligenin phosphate, leptofos.
Other Terms review article
Summary Basal activity levels of the enzyme neuropathy target esterase (NTE) were measured in cultured mouse N2a neuroblastoma cells that had been differentiated for 4 and 8 hours and were found to be 4 μmoles/min/mg protein and 9.23 μmoles/min/mg protein, respectively. The direct-acting organophosphate (OP) phenyl saligenin phosphate (PSP), a compound known to induce a characteristic neuropathy syndrome (OPIDN) in man and animals, used at a concentration of 3 μM that was shown to be non-cytotoxic, produced an almost complete inhibition of NTE of N2a cells after only 4 and 8 hours. NTE activity of N2a cells was also found to be considerably sensitive to inhibition after 4 and 8 hours (inhibition by 57.7% and 66.3%, respectively) to subcytotoxic levels (3 μM) of the pesticide leptofos (LEP), an OP that is needed to be metabolically activated In order to exert in vivo a neuropathic effect. These data suggest that differentiating N2a neuroblastoma cells show promise for use as an in vitro system suitable for the rapid screening of OPIDN-inducing Ops.
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