Quinine inhibits multiple Na+ and K+ transport mechanisms in Ehrlich ascites tumor cells

Smith, Thomas C.; Levinson, Charles

doi:10.1016/0005-2736(89)90512-9

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…The mechanism by which these phenolic compounds act on cells is not yet known. The induction of monovalent cation release from cells by 1 is inhibited, at least partially, by verapamil and quinine. ,, Verapamil, best known as an inhibitor of L-type calcium channels, has direct effects on potassium channels. , Quinine is known to inhibit calcium-activated potassium channels, although it also affects other ion-transport processes …”

Section: Introductionmentioning

confidence: 99%

“…7,8 Quinine is known to inhibit calcium-activated potassium channels, although it also affects other ion-transport processes. 9 The more proximal effect of the active compounds may be mediated by nitric oxide. In vivo studies by Gaginella et al 1 showed that the effect of 5 on water and electrolyte release from the colon was prevented by an inhibitor of nitric oxide synthase (L-NAME) but not by its inactive stereoisomer.…”

Section: Introductionmentioning

confidence: 99%

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Bisphenols That Stimulate Cells To Release Alkali Metal Cations: A Structure−Activity Study

1998

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The laxative action of phenolphthalein (5) is believed to result from induction of potassium and water efflux from the colon epithelium. In cultured cells, K+ efflux is promoted by 5 and by a contaminant (1) present in commercial phenol red. Six compounds with chemical structures related to those of 5 and 1 were tested for ability to induce the release of 86Rb from COS-7 cells preloaded with this isotope: 4,4'-(9-fluorenylidene)diphenol (2), 4, 4'-(9-fluorenylidene)dianiline, 4, 4'-(9-fluorenylidene)bisphenoxyethanol, 1,1'-bi-2-naphthol, 4, 4'-biphenol, and bis(4-hydroxyphenyl)methane. With one exception these compounds were all inactive at a concentration of 10 microM. However, 2 caused profound 86Rb efflux at concentrations as low as 100 nM. Concentrations of 5 1-2 orders of magnitude higher were needed to achieve similar levels of activity. The three compounds known to be active in this experimental system share a common feature that is absent in all the inactive compounds: a five-membered ring structure, one of whose carbon atoms is disubstituted with p-hydroxyphenyl residues. Because 2 and 5 are readily available, comparative studies on the mechanism of action of these biphenols at the cellular level can now be undertaken.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bisphenols That Stimulate Cells To Release Alkali Metal Cations: A Structure−Activity Study

1998

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“…Some studies have provided evidence that quinine blocks CaZ+ -activated K + channels (40,42), but other types of K + channels are also blocked (39,41,43). Quinine may have other effects in some cells (52). Since quinine blocks the agonist-induced inhibition and because the hyperpolarization induced by the preceptor agonist reverses at the K + equilibrium potential, the primary effect of preceptor binding on PVN cells is almost certainly on a K + channel.…”

Section: Discussionmentioning

confidence: 99%

Membrane Properties of Identified Guinea‐Pig Paraventricular Neurons and their Response to an Opioid μ‐Receptor Agonist: Evidence for an Increase in K⁺ Conductance

Kasai¹,

Tasker²,

Jp³

et al. 1993

J Neuroendocrinology

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Intracellular recordings were obtained from neurons in the paraventricular nucleus (PVN) of guinea-pig hypothalamic slices. Passive and active properties of the neurons were determined, and when possible, recorded neurons were injected with biocytin. The effects of a mu-receptor opioid agonist [D-Ala2, Nme-Phe4, Gly5-ol]enkephalin (DAGO) were studied in order to determine which types of cells have mu receptors and to test the hypothesis that an increase in K+ conductance causes mu-receptor-mediated inhibition in the PVN. The recorded cells inside the PVN were divided into two groups, primarily on the basis of the presence or absence of a low threshold Ca2+ spike (LTS). In one group of neurons, LTS potentials could not be evoked (non-LTS cells, n = 42). In another group of neurons (n = 35), LTS potentials with one or two Na+ spikes could be initiated with depolarizing pulses superimposed on steady hyperpolarizing currents; however, these neurons did not fire robust bursts (i.e. non-bursting LTS cells). The mean time constant of non-LTS cells (19.9 +/- 1.6 ms; mean +/- SEM) was significantly shorter than that of non-bursting LTS cells (26.7 +/- 2.1 ms). There were no differences in the mean resting membrane potential, spike amplitude, spike duration, input resistance, spike threshold and pattern of synaptic inputs between the two groups. Intracellular labeling with biocytin combined with cresyl violet counter-staining demonstrated that the two types of cells were located in the PVN.(ABSTRACT TRUNCATED AT 250 WORDS)

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Quinine sensitive changes in cellular Na+ and K+ homeostasis of COS-7 cells caused by a lipophilic phenol red impurity

Hopp¹,

Bunker

Day

1995

In Vitro Cell Dev Biol - Animal

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An impurity of phenol red (PRI) has been shown to markedly alter the intracellular Na+ and K+ homeostasis of several cell types. The effect of PRI seems to involve intracellular Ca(++)-dependent mechanisms. Using COS-7 cells as a model, we further characterized the mechanism of action of PRI by measuring cellular Na+/K+ contents and 86Rb+ efflux. Similar to human skin fibroblasts, in COS-7 cells calmodulin inhibition moderated the cationic transport effects of PRI. A TMB-8 dependent intracellular Ca++ pool does not seem to be involved in these transport events. We found no evidence for participation of the transcriptional-translational machinery in the effect of PRI. Both quinine and quinidine are able to prevent nearly all changes caused by PRI in the cellular Na+/K+ contents and 86Rb+ efflux. Although phenol red contained multiple impurities by high performance liquid chromatography (HPLC), phenolphthalein, a structurally close relative of phenol red, was free of any detectable contamination. Phenolphthalein elicited qualitatively similar transport changes to those observed during exposure to PRI. Regardless of the exact mechanism of action, we propose that the as yet unidentified substance is not a cellular toxin, rather it is a cationic transport modulator. Directly or indirectly, it may interact with the cellular Ca++/calmodulin system and activate some quinine/quinidine sensitive transport processes. This transport process is likely to be a Ca(++)-sensitive K+ channel but, due to the lack of specificity of quinine and quinidine, other transport mechanisms must be also considered. The chemical nature of PRI may be similar to phenolphthalein.

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Quinine inhibits multiple Na+ and K+ transport mechanisms in Ehrlich ascites tumor cells

Cited by 6 publications

References 29 publications

Bisphenols That Stimulate Cells To Release Alkali Metal Cations: A Structure−Activity Study

Bisphenols That Stimulate Cells To Release Alkali Metal Cations: A Structure−Activity Study

Membrane Properties of Identified Guinea‐Pig Paraventricular Neurons and their Response to an Opioid μ‐Receptor Agonist: Evidence for an Increase in K⁺ Conductance

Quinine sensitive changes in cellular Na+ and K+ homeostasis of COS-7 cells caused by a lipophilic phenol red impurity

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Quinine inhibits multiple Na+ and K+ transport mechanisms in Ehrlich ascites tumor cells

Cited by 6 publications

References 29 publications

Bisphenols That Stimulate Cells To Release Alkali Metal Cations: A Structure−Activity Study

Bisphenols That Stimulate Cells To Release Alkali Metal Cations: A Structure−Activity Study

Membrane Properties of Identified Guinea‐Pig Paraventricular Neurons and their Response to an Opioid μ‐Receptor Agonist: Evidence for an Increase in K+ Conductance

Quinine sensitive changes in cellular Na+ and K+ homeostasis of COS-7 cells caused by a lipophilic phenol red impurity

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Membrane Properties of Identified Guinea‐Pig Paraventricular Neurons and their Response to an Opioid μ‐Receptor Agonist: Evidence for an Increase in K⁺ Conductance