scholarly journals The new molecular targets for antidepressants

2021 ◽  
Vol 12 (1) ◽  
pp. 24-32
Author(s):  
Yu. V. Kuznetsov ◽  
D. V. Evdokimov ◽  
I. I. Abramets
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Depressive Disorders ◽  
Regulatory Protein ◽  
Antidepressant Activity ◽  
Membrane Receptors ◽  
Metabotropic Glutamate ◽  
Voltage Dependent ◽  
Depression Disorders ◽  
And Function ◽  
Membrane Density

The efficacy of depressive disorders treatment is insufficient. It is explained by an incomplete understanding of both pathogenesis of depression and antidepressants mechanism action. An improvement of the treatment efficacy of depression disorders is closely associated with complete knowledge of the pathogenesis of disorders and antidepressant mechanism of action. The effect produced by the first line of antidepressants prescribed currently in the clinical practice includes the accumulation of monoamines and prolonged activation of their membrane receptors. However, a decrease in the membrane receptors density evoked by prolonged activation of monoaminergic receptors is counteracted by the second line of antidepressant activity. It is associated with the expression of inducible regulatory protein S100A10 (p11) and its partners. In this review, the authors examined the structure and function of protein p11, its interaction with such proteins as annexin A2, Ahnak, chromatinremodeling factor SMARCA3. The authors analyzed the influence of p11 on the membrane density of serotonin 5-HT1B and 5-HT4 receptors, metabotropic glutamate receptors 5, voltage-dependent potassium Kv3, and calcium Cav1.2 and 1.3 channels, that play an important role in both the effect of antidepressants and the pathogenesis of depression disorders. A systematic literature search was conducted in Scopus, Web of Science, MedLine, elibrary, and other databases.

Persistent current oscillations produced by activation of metabotropic glutamate receptors in immature rat CA3 hippocampal neurons

1995 ◽  
Vol 73 (4) ◽  
pp. 1422-1429 ◽  
Author(s):  
L. Aniksztejn ◽  
M. Sciancalepore ◽  
Y. Ben Ari ◽  
E. Cherubini
Keyword(s):  
Glutamate Receptors ◽  
Hippocampal Neurons ◽  
Metabotropic Glutamate Receptors ◽  
Calcium Release ◽  
Release Process ◽  
Metabotropic Glutamate ◽  
Voltage Dependent ◽  
Inward Currents ◽  
Presynaptic Nerve Terminals ◽  
Calcium Induced Calcium Release

1. The single-electrode voltage-clamp technique was used to study the effects of the metabotropic glutamate receptors (mGluRs) agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, ACPD, 3-10 microM) on CA3 hippocampal neurons during the 1st 10 days of postnatal (P) life and in adulthood. 2. Repeated applications of 1S,3R-ACPD, in the presence of tetrodotoxin (TTX, 1 microM), tetraethylammonium chloride (TEACl 10 mM), and CsCl (2 mM), induced in immature but not in adult neurons periodic inward currents (PICs) that persisted for several hours after the last application of the agonist. 3. PICs, which were generated by nonspecific cationic currents, reversed polarity at 2.8 +/- 3 (SD) mV. They were reversibly blocked by kynurenic acid (1 mM), suggesting that they were mediated by glutamate acting on ionotropic receptors. They were also abolished in a nominally Ca(2+)-free medium. 4. PICs were irreversibly abolished by thapsigargin (10 microM) but were unaffected by ryanodine (10-40 microM). Caffeine (2 mM) also reversibly blocked PICs; this effect was independent from adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, inhibition of voltage-dependent Ca2+ current, or blockade of adenosine receptors. 5. We suggest that, in neonatal slices, mGluRs-induced PICs are triggered by elevation of [Ca2+]i, after mobilization of Ca2+ from inositol 1,4,5-trisphosphate (InsP3)-sensitive stores. This will lead to a persistent, pulsatile release of glutamate from presynaptic nerve terminals, a phenomenon that is probably maintained via a calcium-induced-calcium release process.

Distinct Mechanisms of Presynaptic Inhibition at GABAergic Synapses of the Rat Substantia Nigra Pars Compacta

2005 ◽  
Vol 94 (3) ◽  
pp. 1992-2003 ◽  
Author(s):  
Michela Giustizieri ◽  
Giorgio Bernardi ◽  
Nicola B. Mercuri ◽  
Nicola Berretta
Keyword(s):  
Substantia Nigra ◽  
Presynaptic Inhibition ◽  
Metabotropic Glutamate Receptors ◽  
Calcium Ionophore ◽  
Gaba Release ◽  
Substantia Nigra Pars Compacta ◽  
Gabaergic Neurotransmission ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Voltage Dependent

We investigated the mechanisms of presynaptic inhibition of GABAergic neurotransmission by group III metabotropic glutamate receptors (mGluRs) and GABAB receptors, in dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Both the group III mGluRs agonist l-(+)-2-amino-4-phosphonobutyric acid (AP4, 100 μM) and the GABAB receptor agonist baclofen (10 μM) reversibly depressed the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) to 48.5 ± 2.7 and 79.3 ± 1.6% (means ± SE) of control, respectively. On the contrary, the frequency of action potential-independent miniature IPSCs (mIPSCs), recorded in tetrodotoxin (TTX, 1 μM) and cadmium (100 μM) were insensitive to AP4 but were reduced by baclofen to 49.7 ± 8.6% of control. When the contribution of voltage-dependent calcium channels (VDCCs) to synaptic transmission was boosted with external barium (1 mM), AP4 became effective in reducing TTX-resistant mIPSCs to 65.4 ± 3.9% of control, thus confirming a mechanism of presynaptic inhibition involving modulation of VDCCs. Differently from AP4, baclofen inhibited to 58.5 ± 6.7% of control the frequency mIPSCs recorded in TTX and the calcium ionophore ionomycin (2 μM), which promotes Ca2+-dependent, but VDCC-independent, transmitter release. Moreover, in the presence of α-latrotoxin (0.3 nM), to promote a Ca2+-independent vesicular release of GABA, baclofen reduced mIPSC frequency to 48.1 ± 3.2% of control, while AP4 was ineffective. These results indicate that group III mGluRs depress GABA release to DA neurons of the SNc through inhibition of presynaptic VDCCs, while presynaptic GABAB receptors directly impair transmitter exocytosis.

Glutamate elicits release of BDNF from basal forebrain astrocytes in a process dependent on metabotropic receptors and the PLC pathway

2008 ◽  
Vol 4 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Ying Y. Jean ◽  
Lauren D. Lercher ◽  
Cheryl F. Dreyfus
Keyword(s):  
Basal Forebrain ◽  
Metabotropic Glutamate Receptors ◽  
Cholinergic Neurons ◽  
Metabotropic Receptors ◽  
Western Blots ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Initial Work ◽  
Neuronal Signal ◽  
And Function

A key neurotrophin responsible for the survival and function of basal forebrain (BF) cholinergic neurons is brain-derived neurotrophic factor (BDNF). A number of studies now indicate that a source of this factor may be BF astrocytes. This study was designed to define the role of BF-astrocyte-derived BDNF on cholinergic neurons. Moreover, it investigated regulatory events that modulate BDNF content and release. In initial work BDNF derived from BF-astrocyte-conditioned medium (ACM) was found to increase both numbers of BF acetylcholinesterase (AChE+) cholinergic neurons and the cholinergic synthetic enzyme choline acetyltransferase (ChAT). Western blots, immunocytochemistry and pharmacological inhibition studies revealed that glutamate, through group I metabotropic glutamate receptors (mGluR), increases the intracellular levels of BDNF in BF astrocytes in culture, as well as its release. Furthermore, the release of BDNF is mediated by the actions of PLC, IP3 and internal stores of Ca2+. These results suggest that BF astrocytes serve as local sources of BDNF for cholinergic neurons, and that they may be regulated as such by the neuronal signal, glutamate, through the mediation of group I metabotropic receptors and the PLC pathway.

Expression and Function of Metabotropic Glutamate Receptors in Liver

2007 ◽  
pp. 211-217 ◽  
Author(s):  
Marianna Storto ◽  
Maria Pia Vairetti ◽  
Francesc X. Sureda ◽  
Barbara Riozzi ◽  
Valeria Bruno ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate ◽  
And Function

Imipramine treatment up-regulates the expression and function of mGlu2/3 metabotropic glutamate receptors in the rat hippocampus

2002 ◽  
Vol 42 (8) ◽  
pp. 1008-1015 ◽  
Author(s):  
F Matrisciano ◽  
M Storto ◽  
R.T Ngomba ◽  
I Cappuccio ◽  
A Caricasole ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Rat Hippocampus ◽  
Metabotropic Glutamate ◽  
And Function

scholarly journals Impaired expression and function of group II metabotropic glutamate receptors in pilocarpine-treated chronically epileptic rats

2008 ◽  
Vol 1240 ◽  
pp. 165-176 ◽  
Author(s):  
Emilio R. Garrido-Sanabria ◽  
Luis F. Pacheco Otalora ◽  
Massoud F. Arshadmansab ◽  
Berenice Herrera ◽  
Sebastian Francisco ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate ◽  
Group Ii ◽  
And Function

Anatomy and function of group III metabotropic glutamate receptors in gastric vagal pathways

2008 ◽  
Vol 54 (6) ◽  
pp. 965-975 ◽  
Author(s):  
Richard L. Young ◽  
Nicole J. Cooper ◽  
L. Ashley Blackshaw
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
And Function

scholarly journals Interaction of glutamate- and adenosine-induced decrease of acetylcholine quantal release at frog neuromuscular junction

2010 ◽  
pp. 803-810
Author(s):  
S Adámek ◽  
AV Shakirzyanova ◽  
AI Malomouzh ◽  
NV Naumenko ◽  
F Vyskočil
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Inhibitory Effect ◽  
No Production ◽  
Frog Neuromuscular Junction ◽  
Quantal Release ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Voltage Dependent ◽  
Endplate Potentials

In a frog neuromuscular preparation of m. sartorius, glutamate had a reversible dose-dependent inhibitory effect on both spontaneous miniature endplate potentials (MEPP) and nerve stimulation-evoked endplate potentials (EPP). The effect of glutamate on MEPP and EPP is caused by the activation of metabotropic glutamate receptors, as it was eliminated by MCPG, an inhibitor of group I metabotropic glutamate receptors. The depression of evoked EPP, but not MEPP frequency was removed by inhibiting the NO production in the muscle by L-NAME and by ODQ that inhibits the soluble NO-sensitive guanylyl cyclase. The glutamate-induced depression of the frequency of spontaneous MEPP is apparently not caused by the stimulation of the NO cascade. The particular glutamate-stimulated NO cascade affecting the evoked EPP can be down-regulated also by adenosine receptors, as the glutamate and adenosine actions are not additive and application of adenosine partially prevents the further decrease of quantal content by glutamate. On the other hand, there is no obvious interaction between the glutamatemediated inhibition of EPP and inhibitory pathways triggered by carbacholine and ATP. The effect of glutamate on the evoked EPP release might be due to NO-mediated modulation (phosphorylation) of the voltage-dependent Ca2+ channels at the presynaptic release zone that are necessary for evoked quantal release and open during EPP production.

Modulation of regenerative membrane properties by stimulation of metabotropic glutamate receptors in rat deep dorsal horn neurons

1996 ◽  
Vol 76 (4) ◽  
pp. 2794-2798 ◽  
Author(s):  
V. Morisset ◽  
F. Nagy
Keyword(s):  
Glutamate Receptors ◽  
Dorsal Horn ◽  
Metabotropic Glutamate Receptors ◽  
Firing Frequency ◽  
Membrane Properties ◽  
Cervical Region ◽  
Metabotropic Glutamate ◽  
Dorsal Horn Neurons ◽  
Voltage Dependent

1. Intracellular recordings were obtained from 111 dorsal horn neurons in lamina V, in an in vitro transverse spinal cord slice preparation of the cervical region from young rats. 2. Of these neurons, 28% showed voltage-dependent plateau potentials, mainly underlain by a tetrodotoxin-resistant dihydropyridine-sensitive Ca2+ current. When depolarized, neurons with plateau properties produced accelerating firing frequency, afterdischarge, and bistability. They also exhibited windup of action potentials when stimulated by repetitive intracellular injections of current. 3. Glutamate being the main excitatory transmitter released by primary afferents, we also considered the effects of specific agonists of metabotropic glutamate receptors and showed that they modulate positively (induce or enhance) plateau properties in the deep dorsal horn neurons.

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