Studies of the potency of protein kinase inhibitors on ATPase activities

Barret, Jean-Marc; Ernould, Anne-Pascale; Rouillon, Marie-Hélène; Ferry, Gilles; Genton, Annie; Boutin, Jean A.

doi:10.1016/0009-2797(93)90108-b

Cited by 15 publications

(6 citation statements)

References 42 publications

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“…This compound displayed additional (side‐) effects on neuronal activity in our slice and MEA recordings: a slow and irreversible inhibition of firing. It is not clear whether this was related to P2Y receptors or other actions, such as inhibition of ATPase activity (Barret et al ., 1993), stimulation of mitochondrial Ca 2+ uptake (Schoff, 1995), inhibition of adenine nucleotide translocase and mitochondrial inner membrane anion channels (Beavis, 1992).…”

Section: Discussionmentioning

confidence: 99%

P2Y receptor‐mediated excitation in the posterior hypothalamus

Sergeeva

Klyuch

Fleischer

et al. 2006

Eur J of Neuroscience

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Histaminergic neurons located in the posterior hypothalamus (tuberomamillary nucleus, TMN) project widely through the whole brain controlling arousal and attention. They are tonically active during wakefulness but cease firing during sleep. As a homeostatic theory of sleep involves ATP depletion and adenosine accumulation in the brain, we investigated the role of ATP and its analogues as well as adenosine on neuronal activity in the TMN. We show increased firing of rat TMN neurons by ATP, ADP, UTP and 2meSATP, indicating activation of receptors belonging to the P2Y family. Adenosine affected neither membrane potential nor firing of these cells. Single-cell reverse transcriptase-polymerase chain reaction revealed that P2Y1 and P2Y4 are prevailing receptors in TMN neurons. P2Y1 receptor mRNA was detected with a higher frequency in 2-week-old than in 4-week-old rats; in accordance, 2meSATP was more potent than ATP. Semi-quantitative real-time polymerase chain reaction revealed a developmental downregulation of mRNA levels for P2Y1 and P2Y4 receptors. Immunocytochemistry demonstrated neuronal and glial localization of the P2Y1 receptor protein. Network activity measured with multielectrode arrays in primary cultures made from the posterior hypothalamus was enhanced by UTP and 2meSATP (P2Y4 and P2Y1 agonists, respectively). ATP caused an inhibition of firing, which was reversed in the presence of suramin or gabazine [gamma-aminobutyric acid (GABA)A receptor antagonist], indicating that GABAergic neurons are preferentially activated by ATP in this network. Excitation of the wake-active TMN neurons by nucleotides and the lack of adenosine action may be important factors in sleep-wake regulation.

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Section: Discussionmentioning

confidence: 99%

P2Y receptor‐mediated excitation in the posterior hypothalamus

Sergeeva

Klyuch

Fleischer

et al. 2006

Eur J of Neuroscience

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“…PKs not only reveal similar structures consisting of a catalytic kinase domain fused with varying sets of protein-protein interaction and membrane association domains, but they all share the same catalytic mechanism, the transfer of the terminal phosphate from ATP to a substrate molecule [118]. Owing to their high degree of homology, it was controversially debated in the past whether selective inhibition can be achieved, especially with respect to drug development and medication [119,120]. For instance, Genistein, described as a specific protein tyrosine kinase (PTK) inhibitor in 1987 [121], was later reported to be active as an inhibitor of topoisomerase II [122], another class of ATP-dependent enzymes, a feature also attributed to Erbstatin [123].…”

Section: Pk Inhibitorsmentioning

confidence: 98%

Protein Kinases as Potential Targets for Novel Anti-Schistosomal Strategies

Beckmann

Leutner²,

Gouignard³

et al. 2012

cpd

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Schistosome parasites are the causative pathogens of schistosomiasis (bilharzia), a disease of worldwide significance. In terms of patient numbers, schistosomiasis ranks second to malaria as a parasitosis affecting more than 200 million people of the tropics and subtropics. Since the 1970s Praziquantel (PZQ) is the drug of choice and nearly exclusively used for treatment. However, drug resistance is an increasing threat, particularly with respect to large-scale PZQ administration programs. Last decade´s research indicated that resistance against PZQ can be induced under laboratory conditions, and field studies provided first indications for the possibility of reduced PZQ efficacy. Furthermore, clear evidence for the molecular armamentarium of schistosomes with multidrug transporters was found, one of which was responding to PZQ challenge. Also the development of a vaccine still represents an elusive goal, although effort and time have been invested in this subject. In light of these facts it is commonly accepted that new drugs are urgently needed. Research on signal transduction processes in Schistosoma mansoni has provided an unexpected and novel perspective towards this end. Molecular, biochemical, and physiological studies elucidating principles of schistosome development have demonstrated the essential role of protein kinases (PKs). In humans, PKs are known to be involved in cancer development. Since a variety of approved anticancer drugs targeting PKs exist, first studies have been performed to investigate whether these drugs are able to also inhibit schistosome PKs. Indeed, promising results have been obtained indicating the potential of PKs as privileged targets for new concepts in fighting schistosomes.

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“…They bind to MF 1 and inhibit ATPase activity (28,297). BzAF contains a benzophenone moiety on one side of the molecule that is excitable by irradiation at ϳ340 to 366 nm, and the irradiation of BzaF leads to the covalent insertion of BzAF into F 1 .…”

Section: Purine Nucleotides and Nucleotide Analogsmentioning

confidence: 99%

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

Hong

Pedersen

2008

Microbiol Mol Biol Rev

272

302

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SUMMARY ATP synthase, a double-motor enzyme, plays various roles in the cell, participating not only in ATP synthesis but in ATP hydrolysis-dependent processes and in the regulation of a proton gradient across some membrane-dependent systems. Recent studies of ATP synthase as a potential molecular target for the treatment of some human diseases have displayed promising results, and this enzyme is now emerging as an attractive molecular target for the development of new therapies for a variety of diseases. Significantly, ATP synthase, because of its complex structure, is inhibited by a number of different inhibitors and provides diverse possibilities in the development of new ATP synthase-directed agents. In this review, we classify over 250 natural and synthetic inhibitors of ATP synthase reported to date and present their inhibitory sites and their known or proposed modes of action. The rich source of ATP synthase inhibitors and their known or purported sites of action presented in this review should provide valuable insights into their applications as potential scaffolds for new therapeutics for human and animal diseases as well as for the discovery of new pesticides and herbicides to help protect the world's food supply. Finally, as ATP synthase is now known to consist of two unique nanomotors involved in making ATP from ADP and Pi, the information provided in this review may greatly assist those investigators entering the emerging field of nanotechnology.

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Studies of the potency of protein kinase inhibitors on ATPase activities

Cited by 15 publications

References 42 publications

P2Y receptor‐mediated excitation in the posterior hypothalamus

P2Y receptor‐mediated excitation in the posterior hypothalamus

Protein Kinases as Potential Targets for Novel Anti-Schistosomal Strategies

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

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