A modulation of glutamate-induced phosphoinositide breakdown by intracellular pH changes

Vignes, Michel; Blanc, Emmanuel; Guiramand, Janique; González, Elsa Marina Álvarez; Sassetti, Isabelle; Récasens, Max

doi:10.1016/s0028-3908(96)00102-5

Cited by 9 publications

(4 citation statements)

References 27 publications

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“…These sites may represent an additional imidazoline receptor population that is distinct from previously identified I 1 -and I 2 -subtypes (85). Several lines of evidence suggest that intracellular free protons have properties of second messengers in addition to a role in receptor and enzyme regulation (163,168). Moreover, essential neurotransmitters (i.e., GABA, glutamate and norepinephrine) induce transient and moderate changes of pH-values in neurons (75,90,155) and neurotransmitter release can be influenced by intracellular free protons (166).…”

Section: Table 3 Cerebral Adaptive Effects Of Chronic Administrationmentioning

confidence: 87%

Moclobemide: Evolution, Pharmacodynamic, and Pharmacokinetic Properties

Bonnet¹

2002

CNS Drug Reviews

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The benzamide moclobemide is a reversible inhibitor of monoamine-oxidase-A (RIMA). It has been extensively evaluated in the treatment of a wide spectrum of depressive disorders and less extensively in anxiety disorders. While clinical aspects will be presented in a subsequent review, this article focuses primarily on moclobemide's evolution, pharmacodynamic and pharmacokinetic properties. In particular, the effects on neurotransmission and intracellular signal transduction, the neuroendocrine system, the tyramine pressure response and animal models of depression are surveyed. In addition, other CNS effects are reviewed with special respect to experimental serotonergic syndrome, anxiolytic and antinociceptive activity, sleep, cognition and driving performance, neuroprotection and seizures.

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Section: Table 3 Cerebral Adaptive Effects Of Chronic Administrationmentioning

confidence: 87%

Moclobemide: Evolution, Pharmacodynamic, and Pharmacokinetic Properties

Bonnet¹

2002

CNS Drug Reviews

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“…These findings support the idea that some antiepileptics and antidepressants may have a therapeutic impact via pHi‐changes. A moderate decrease in the pH i could lower aberrant intracellular signalling (Vignes et al. , 1996), for example, and this would have a favourable effect in critical regions of the limbic forebrain and temporal lobes, where hyperexcitability is evident in temporal lobe seizures (Koehling et al.…”

Section: Discussionmentioning

confidence: 99%

Modulatory effects of neuropsychopharmaca on intracellular pH of hippocampal neurones in vitro

Bonnet

Bingmann

Wiltfang

et al. 2010

British J Pharmacology

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Background and purpose:The intracellular pH (pHi) of neurones is tightly regulated by, for example, membrane-bound acid-exchangers and loaders. Nevertheless, excessive bioelectric activity lowers steady-state pHi. In turn, even a moderate acidification can inhibit neuronal activity, a process believed to be part of a negative feedback loop controlling neuronal excitation. As moclobemide, an antidepressant, and also some antiepileptic drugs can reduce neuronal pHi in hippocampus slices in vitro, we screened a panel of currently used neuropsychopharmaca for comparable effects. Experimental approach: BCECF-AM loaded hippocampal slices were superfused with 16 different neuroleptics, antidepressants and antiepileptics under bicarbonate-buffered conditions. Changes in steady-state pHi of CA3 neurones were measured fluorometrically. Key results: The antipsychotics haloperidol, clozapine, ziprasidone, and the antidepressants amitriptyline, doxepin, trimipramine, citalopram, mirtazapine, as well as the anticonvulsive drug tiagabine reversibly reduced the steady-state pHi by up to 0.35 pH-units in concentrations of 5-50 mM. In contrast, venlafaxine, the anticonvulsants carbamazepine, clonazepam, gabapentin, lamotrigine, zonisamide, and the mood stabilizer lithium had no effect on neuronal pHi. Conclusion and implications:These data substantiate the view that clinically relevant concentrations of neuroleptics and antidepressants can mediate changes in neuronal pHi, which may contribute to their pharmacological mode of action. Effects on pHi should be taken into account when therapeutic or even harmful effects of these drugs are evaluated.

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“…Firstly, as noted in the Introduction, neuronal ionic conductances (Daumas & Andersen, 1993; Tombaugh & Somjen, 1997) and the activities of intracellular enzymes (e.g. Vignes et al 1996) are sensitive to shifts in pH i , as are the activities of transport and buffering mechanisms for various ions (e.g. Zucker, 1981; Dipolo & Beaugé, 1982; Sidky & Baimbridge, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Changes in pH i evoked by amino acid neurotransmitters may, in turn, represent a physiologically important facet of their mechanism of action given that neuronal ionic conductances, the activities of intracellular second messenger systems, and buffering and transport mechanisms for various intracellular ions are all sensitive to changes in pH i (e.g. Dipolo & Beaugé, 1982; Daumas & Andersen, 1993; Vignes et al 1996; Tombaugh & Somjen, 1997).…”

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confidence: 99%

Effects of noradrenaline on intracellular pH in acutely dissociated adult rat hippocampal CA1 neurones

Smith

Brett

Church

1998

The Journal of Physiology

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1. We examined the effects of noradrenaline on steady-state intracellular pH (pHé) and the recovery of pHé from internal acid loads imposed by the NHÚ¤ prepulse technique in hippocampal CA1 neurones acutely dissociated from adult rats. 2. Under nominally HCO×¦-free conditions, acid extrusion was accomplished by a Na¤-dependent mechanism, probably the amiloride-insensitive variant of the Na¤-H¤ exchanger previously characterized in both fetal and adult rat hippocampal neurones. In the presence of external HCO×¦, acid extrusion appeared to be supplemented by a Na¤-dependent HCO×¦-Cl¦ exchanger, the activity of which was dependent upon the absolute level of pHé. 3. Noradrenaline evoked a concentration-dependent and sustained rise in steady-state pHé and increased rates of pHé recovery from imposed intracellular acid loads. The effects of noradrenaline were not dependent upon the presence of external HCO×¦ but were blocked by substituting external Na¤ with N-methyl-d-glucamine, suggesting that noradrenaline acts to increase steady-state pHé by increasing the activity of the Na¤-H¤ exchanger. 4. The effects of noradrenaline on steady-state pHé and on rates of pHé recovery from imposed acid loads were mimicked by â1-and âµ-, but not á-, adrenoceptor agonists. The â_adrenoceptor antagonist propranolol blocked the ability of noradrenaline to increase both steady-state pHé and rates of pHé recovery from acid loads. 5. The effects of noradrenaline on steady-state pHé and on pHé recovery rates following acid loads were not dependent on changes in [Ca¥]é. However, the effects of noradrenaline were blocked by pre-treatment with the adenylate cyclase inhibitor 2',5'-dideoxyadenosine and the cAMP-dependent protein kinase inhibitors Rp-adenosine-3',5'-cyclic monophosphorothioate (sodium salt; Rp-cAMPS) and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide (H-89). 6. Forskolin, an activator of endogenous adenylate cyclase, and 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, mimicked the ability of noradrenaline to increase both steadystate pHé and rates of pHé recovery from imposed acid loads, as did Sp-cAMPS, a selective activator of cAMP-dependent protein kinase. The effect of forskolin on steady-state pHé was blocked by pre-treatment with Rp-cAMPS whereas the effect of Sp-cAMPS was enhanced by pre-treatment with the protein phosphatase inhibitor, okadaic acid. 7. Noradrenaline also increased steady-state pHé and rates of pHé recovery from imposed acid loads in cultured postnatal rat hippocampal neurones. In this preparation, the effects of noradrenaline were occluded by 18-24 h pre-treatment with cholera toxin. 8. We conclude that noradrenaline increases the activity of the Na¤-H¤ exchanger in rat hippocampal neurones, probably by inducing an alkaline shift in the pHé dependence of the antiport, thereby raising steady-state pHé. The effects of noradrenaline are mediated by â_adrenoceptors via a pathway which involves the á-subunit of the stimulatory G-protein Gs (Gsá), adenylate cyclase, cAMP and the su...

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A modulation of glutamate-induced phosphoinositide breakdown by intracellular pH changes

Cited by 9 publications

References 27 publications

Moclobemide: Evolution, Pharmacodynamic, and Pharmacokinetic Properties

Moclobemide: Evolution, Pharmacodynamic, and Pharmacokinetic Properties

Modulatory effects of neuropsychopharmaca on intracellular pH of hippocampal neurones in vitro

Effects of noradrenaline on intracellular pH in acutely dissociated adult rat hippocampal CA1 neurones

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