Inhibitors of tissue-nonspecific alkaline phosphatase: Design, synthesis, kinetics, biomineralization and cellular tests

Debray, Julien; Chang, Lei; Marquès, Stéphanie; Pellet‐Rostaing, Stéphane; Do, Le-Duy; Mébarek, Saida; Buchet, René; Magne, David; Popowycz, Florence; Lemaire, Marc

doi:10.1016/j.bmc.2013.09.053

Cited by 32 publications

(22 citation statements)

References 44 publications

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“…The IC 50 we report here were 730 µM for antidromic response and 410 µM for orthodromic responses. Both values are much larger than those reported for TNAP inhibition by levamisole in biochemical assays on cell extracts or on cells cultures-in the range of 10-70 µM (Van Belle 1972, 1976aGoldstein et al 1980;Anagnostou et al 1996;Picher et al 2003;Sergienko and Millán 2010;Debray et al 2013), including brain cell extracts (IC 50 = 44 µM in Calhau et al 2000). In addition the exponent of the Hill equation fitted to our data was close to 3, whereas TNAP inhibition has a Hill coefficient close to 1 (Suzuki et al 1994).…”

Section: Suppression Of Neuronal Activity By Tetramisole and Levamisocontrasting

confidence: 62%

“…In addition, the IC 50 for neuronal response suppression by tetramisole (Fig. 12.2c, d) was much higher than that expected given the IC 50 values reported for TNAP inhibition by levamisole or tetramisole in biochemical assays on cell extracts or cell cultures (Van Belle 1972, 1976a, 1976bGoldstein et al 1980;Anagnostou et al 1996;Calhau et al 2000;Picher et al 2003;Sergienko and Millán 2010;Debray et al 2013): the IC 50 that has been reported in these studies is between 10 and 70 µM. In addition, the slope of the Hill equation fitted to our data was close to 3, while a Hill coefficient value close to 1 has been reported for the inhibition of TNAP by levamisole (Suzuki et al 1994).…”

Section: The Effect Of Tetramisole Is Not Stereo-specificmentioning

confidence: 69%

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Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex

Nowak

Rosay

Czégé

et al. 2015

Subcellular Biochemistry

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Tissue non-specific alkaline phosphatase (TNAP) may be involved in the synthesis of GABA and adenosine, which are the main inhibitory neurotransmitters in cortex. We explored this putative TNAP function through electrophysiological recording (local field potential ) in slices of mouse somatosensory cortex maintained in vitro. We used tetramisole, a well documented TNAP inhibitor, to block TNAP activity. We expected that inhibiting TNAP with tetramisole would lead to an increase of neuronal response amplitude, owing to a diminished availability of GABA and/or adenosine. Instead, we found that tetramisole reduced neuronal response amplitude in a dose-dependent manner. Tetramisole also decreased axonal conduction velocity. Levamisole had identical effects. Several control experiments demonstrated that these actions of tetramisole were independent from this compound acting on TNAP. In particular, tetramisole effects were not stereo-specific and they were not mimicked by another inhibitor of TNAP, MLS-0038949. The decrease of axonal conduction velocity and preliminary intracellular data suggest that tetramisole blocks voltage-dependent sodium channels. Our results imply that levamisole or tetramisole should not be used with the sole purpose of inhibiting TNAP in living excitable cells as it will also block all processes that are activity-dependent. Our data and a review of the literature indicate that tetramisole may have at least four different targets in the nervous system. We discuss these results with respect to the neurological side effects that were observed when levamisole and tetramisole were used for medical purposes, and that may recur nowadays due to the recent use of levamisole and tetramisole as cocaine adulterants.

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Section: Suppression Of Neuronal Activity By Tetramisole and Levamisocontrasting

confidence: 62%

Section: The Effect Of Tetramisole Is Not Stereo-specificmentioning

confidence: 69%

Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex

Nowak

Rosay

Czégé

et al. 2015

Subcellular Biochemistry

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“…This unique reversibility minimizes long-term toxicity of the nanofibrils, thus warranting pNDP1 as a cell compatible activity probe for imaging the activities of ALPs on live cells. Moreover, after pre-treating HeLa cells with (−)-tetramisole (40 μM), an inhibitor of tissue-non-specific ALP (ALPL) 31 , and imaging the cells incubated with pNDP1 together with (−)-tetramisole (40 μM) for 3 hours, we found little difference (Fig. S2c) in the images of HeLa cells with and without the addition of (−)-tetramisole.…”

Section: Resultsmentioning

confidence: 98%

Enzyme-Instructed Self-Assembly for Spatiotemporal Profiling of the Activities of Alkaline Phosphatases on Live Cells

Zhou

Berciu

et al. 2016

Chem

154

146

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Summary Alkaline phosphatase (ALP), an ectoenzyme, plays important roles in biology. But there is no activity probes for imaging ALPs in live cell environment due to the diffusion and cytotoxicity of current probes. Here we report the profiling of the activities of ALPs on live cells by enzyme-instructed self-assembly (EISA) of a D-peptidic derivative that forms fluorescent, non-diffusive nanofibrils. Our study reveals the significantly higher activities of ALP on cancer cells than on stromal cells in their co-culture and shows an inherent and dynamic difference in ALP activities between drug sensitive and resistant cancer cells or between cancer cells with and without hormonal stimulation. Being complementary to genomic profiling of cells, EISA, as a reaction-diffusion controlled process, achieves high spatiotemporal resolution for profiling activities of ALPs of live cells at single cell level. The activity probes of ALP contribute to understanding the reversible phosphorylation/dephosphorylation in the extracellular domains that is an emerging frontier in biomedicine.

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“…The role of BALP as a key player in the mineralization process of bone and soft tissue renders it a possible treatment target for the prevention of CV disease, and investigations to identify possible therapeutic TNAP inhibitors are ongoing (249,262). We have previously demonstrated catalytic differences between the BALP isoforms with respect to the inactivation of the calcification inhibitor PPi.…”

Section: Balp Isoforms In the Development Of Inhibitors Of Vascular Cmentioning

confidence: 99%

Bone alkaline phosphatase isoforms in chronic kidney disease : mineral and bone disorder

Haarhaus

2014

Linköping University Medical Dissertations

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Inhibitors of tissue-nonspecific alkaline phosphatase: Design, synthesis, kinetics, biomineralization and cellular tests

Cited by 32 publications

References 44 publications

Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex

Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex

Enzyme-Instructed Self-Assembly for Spatiotemporal Profiling of the Activities of Alkaline Phosphatases on Live Cells

Bone alkaline phosphatase isoforms in chronic kidney disease : mineral and bone disorder

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