Binding of psychoactive drugs to rat brain amine receptors, measured ex vivo, and their effects on the metabolism of biogenic amines

Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and with biochemical and animal-behavioural properties which are strikingly different from those of classical tricyclics. Unlike the latter, which decrease serotonin (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.g. fluoxetine) have opposite effects. On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other tricyclics prolong it, and it enhances attention, learning, and memory in laboratory animals, while classical tricyclics have opposite effects. However, the relationships between these effects of tianeptine in animal experiments and their relevance to clinical findings remain to be determined.

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THE INFLUENCE OF ANTIPSYCHOTIC DRUGS ON METABOLITES OF BIOGENIC AMINES IN DIFFERENT PARTS OF THE RAT BRAIN COMPARED TO BEHAVIOURAL CHANGES

Abstracts ◽

10.1016/b978-0-08-021308-8.51195-9 ◽

1977 ◽

pp. 497

Author(s):

Manfred Ackenheil ◽

Johannes Zimmermann ◽

Barbara von Stralendorff

Keyword(s):

Rat Brain ◽

Biogenic Amines ◽

Antipsychotic Drugs ◽

Behavioural Changes ◽

Different Parts

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Autoradiographic Studies on the Distribution of Psychoactive Drugs in the Rat Brain

International Pharmacopsychiatry ◽

10.1159/000468836 ◽

1969 ◽

Vol 2 (1-2) ◽

pp. 12-26 ◽

Cited By ~ 6

Author(s):

H. Eckert ◽

A. Hopf

Keyword(s):

Rat Brain ◽

Psychoactive Drugs

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PKA at a Cross-Road of Signaling Pathways Involved in the Regulation of Glioblastoma Migration and Invasion by the Neuropeptides VIP and PACAP

Cancers ◽

10.3390/cancers11010123 ◽

2019 ◽

Vol 11 (1) ◽

pp. 123 ◽

Cited By ~ 2

Author(s):

Souheyla Bensalma ◽

Soumaya Turpault ◽

Annie-Claire Balandre ◽

Madryssa De Boisvilliers ◽

Afsaneh Gaillard ◽

...

Keyword(s):

Rat Brain ◽

Ex Vivo ◽

Brain Parenchyma ◽

Migration And Invasion ◽

C6 Cells ◽

Selective Inhibitors ◽

Receptor System ◽

And Migration ◽

Vip Receptor

Glioblastoma (GBM) remains an incurable disease, mainly due to the high migration and invasion potency of GBM cells inside the brain. PI3K/Akt, Sonic Hedgehog (SHH), and PKA pathways play major regulatory roles in the progression of GBM. The vasoactive intestinal peptide (VIP) family of neuropeptides and their receptors, referred in this article as the “VIP-receptor system”, has been reported to regulate proliferation, differentiation, and migration in a number of tumor cell types and more particularly in GBM cells. These neuropeptides are potent activators of the cAMP/PKA pathway. The present study aimed to investigate the cross-talks between the above cited signaling cascades. Regulation by VIP-related neuropeptides of GBM migration and invasion was evaluated ex vivo in rat brain slices explanted in culture. Effects of different combinations of VIP-related neuropeptides and of pharmacological and siRNA inhibitors of PKA, Akt, and of the SHH/GLI1 pathways were tested on GBM migration rat C6 and human U87 GBM cell lines using the wound-healing technique. Quantification of nuclear GLI1, phospho-Akt, and phospho-PTEN was assessed by western-immunoblotting. The VIP-receptor system agonists VIP and PACAP-38 significantly reduced C6 cells invasion in the rat brain parenchyma ex vivo, and C6 and U87 migration in vitro. A VIP-receptor system antagonist, VIP10-28 increased C6 cell invasion in the rat brain parenchyma ex vivo, and C6 and migration in vitro. These effects on cell migration were abolished by selective inhibitors of the PI3K/Akt and of the SHH pathways. Furthermore, VIP and PACAP-38 reduced the expression of nuclear GLI1 while VIP10-28 increased this expression. Selective inhibitors of Akt and PKA abolished VIP, PACAP-38, and VIP10-28 effects on nuclear GLI1 expression in C6 cells. PACAP-38 induced a time-dependent inhibition of phospho-Akt expression and an increased phosphorylation of PTEN in C6 cells. All together, these data indicate that triggering the VIP-receptor system reduces migration and invasion in GBM cells through a PKA-dependent blockade of the PI3K/Akt and of the SHH/GLI1 pathways. Therefore, the VIP-receptor system displays anti-oncogenic properties in GBM cells and PKA is a central core in this process.

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