Signal-transducing G proteins and antidepressant Drugs: Evidence for modulation of α subunit gene expression in rat brain

Lesch, Klaus‐Peter; Manji, Husseini K.

doi:10.1016/0006-3223(92)90070-g

Cited by 79 publications

(28 citation statements)

References 51 publications

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“…Chronic treatment with TCAs induces an increase in the Go-protein levels in different rat brain regions, such as frontal cortex, midbrain and hypothalamus (Lesch et al 1991;Lesch and Manji 1992). Moreover, Yamamoto et al (1992) reported that several TCAs, including clomipramine, were able to increase, in a PTX-dependent manner, the GTPase activity of Go proteins, purified from bovine brain membranes, indicating the ability of these compounds to directly stimulate Go proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Contrary to Gs-proteins, the role of Giproteins in the mechanism of action of antidepressant drugs is more controversial. Chronic treatment with antidepressant drugs has been reported to produce a reduction of Gi ␣ and an increase of the Go ␣ protein levels (Lesch et al 1991;Lesch and Manji 1992;Raap et al 1999) in various regions of rat brain, including neostriatum, hypothalamus, frontal cortex and midbrain. By contrast, no alteration of Gi ␣ and Go ␣ protein and mRNA levels in rat brain (cortex, hippocampus, cerebellum) was observed after chronic treatment with tricyclic antidepressants (TCA) and monoamine oxidase inhibitors (Li et al 1993;Chen and Rasenick 1995;Emamghoreishi et al 1996;Dwivedi and Pandey 1997).…”

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confidence: 99%

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Role of Gi Proteins in the Antidepressant-like Effect of Amitriptyline and Clomipramine

Galeotti

Bartolini

Ghelardini

2002

Neuropsychopharmacology

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The effect of the i.c.v. administration of pertussis toxin (PTX) and antisense oligodeoxynucleotides directed against the ␣ subunit of different Gi-proteins (anti-For the past several decades, antidepressant drugs have been widely used in the treatment of clinical depression and other psychiatric disorders. Several distinct pharmacological compounds show therapeutic efficacy. These include monoamine oxidase inhibitors, tricyclic compounds, selective serotonin and norepinephrine reuptake inhibitors, as well as some atypical drugs. Numerous studies have examined the effects of antidepressants on neurotransmitter metabolism, turnover, and receptor sensitivity and several theories on their mechanism of action have been proposed. These include the inhibition of monoamine transporter activity in presynaptic membranes (Schildkraut 1965), downregulation of ␤ -adrenoceptors (Mazzola-Pomietto et al. 1994), alteration at cholinergic, dopaminergic or GABAergic receptors (Henringer and Charney 1987). However, the molecular mechanism of action underlying the therapeutic effect of antidepressants is still unclear.Despite their diversity, these treatments subserve the same final clinical effect. Therefore, the possibility that these diverse agents converge on a single postreceptorial target evoked a great research interest. Since most neurotransmitter receptors and neuromodulators are coupled to intracellular effectors through G-proteins (Birnbaumer 1990), recent studies searching for a com-

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Role of Gi Proteins in the Antidepressant-like Effect of Amitriptyline and Clomipramine

Galeotti

Bartolini

Ghelardini

2002

Neuropsychopharmacology

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“…99 Otro estudio con PCR convencional muestra que la imipramina y la fluoxetina no tienen efecto sobre la expresión de G αs G αi1/2 , G αo y G αq en la corteza frontal y el hipocampo, pero sí un aumento significativo sólo en G α12 . 101 Desde hace tres décadas se conoce que los antidepresivos provocan la regulación a la baja de los receptores β-adrenérgicos 102 o de otros receptores acoplados a G s (v. gr. 5-HT 4 , 5-HT 6 ).…”

Section: B) Efecto Sobre La Expresión De Las Proteínas Gunclassified

Neurobiología de la depresión mayor y de su tratamiento farmacológico

Hernández

Coronel

Aguilar

et al. 2016

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“…These results suggest that imipramine and corticosterone treatments modify neither the number of receptors nor their binding properties but they influence in an opposite manner the signaling cascades downstream the receptor. These modifications are likely to involve changes in the capacity of the receptor to activate G protein and/or changes in G protein expression or phosphorylation [15,50,69]. These data are consistent with the results obtained by other investigators who demonstrated that multiple ECS, lithium and fluoxetine reduced the quantity of mRNA for the a subunit of the Gs protein in the CA1 hippcampal area [48,59], while fluoxetine, imipramine, clomipramine, desimipramine and clorgyline also reduced the protein amount of the a subunit of the Gs [50,49].…”

Section: +mentioning

confidence: 99%

Stress- and antidepressant treatment-induced modifications of 5-HT7 receptor functions in the rat brain

Tokarski

Bobula

Grzegorzewska-Hiczwa

et al. 2012

Pharmacological Reports

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Abstract:This paper summarizes a series of electrophysiological studies aimed at finding the effects of the activation of 5-HT 7 receptors on neuronal excitability as well as on excitatory and inhibitory synaptic transmission in the hippocampus and in the frontal cortex of the rat. These studies demonstrated that 5-HT 7 receptors play an important role in the modulation of the activity of the hippocampal network by regulating the excitability of pyramidal cells of the CA1 area, as well as via their effect on GABA and glutamatergic transmission. The reactivity of 5-HT 7 receptors in the hippocampus is decreased by repeated administration of antidepressant drugs and increased by a prolonged high level of corticosterone. More importantly, administration of antidepressant drug, imipramine, prevents the occurrence of corticosterone-induced changes in the function of hippocampal 5-HT 7 receptors. It has also been found that the blockade of 5-HT 7 receptors by the selective antagonist SB 269970, lasting for a few days, causes similar changes to those observed after long-term administration of antidepressants. Thus, it seems that the pharmacological blockade of 5-HT 7 receptors produces faster effects compared to classic antidepressant drugs. A similarity between the changes in the glutamatergic transmission induced by the blockade of 5 HT 7 receptors and those caused by repeated administration of the antidepressant drug, imipramine, has also been found in the frontal cortex. It has also been shown that the changes in glutamatergic transmission and the impairment of long-term synaptic plasticity in the frontal cortex of animals subjected to repeated restraint stress are reversed by the blockade of 5-HT 7 receptors. Overall, these studies, together with the data provided by other investigators, support the hypothesis that 5-HT 7 receptor antagonists may become a prototype of a new class of antidepressant drugs. Such compounds will not function by blocking 5-HT reuptake, as many of the currently used drugs, but through a direct interaction with the 5-HT 7 receptor. This type of action is highly selective and usually does not require the occurrence of adaptive changes in neuronal functions, thus allowing for a much quicker therapeutic effect.

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Signal-transducing G proteins and antidepressant Drugs: Evidence for modulation of α subunit gene expression in rat brain

Cited by 79 publications

References 51 publications

Role of Gi Proteins in the Antidepressant-like Effect of Amitriptyline and Clomipramine

Role of Gi Proteins in the Antidepressant-like Effect of Amitriptyline and Clomipramine

Neurobiología de la depresión mayor y de su tratamiento farmacológico

Stress- and antidepressant treatment-induced modifications of 5-HT7 receptor functions in the rat brain

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