Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor

Eisensamer, B.; Rammes, Gerhard; Gimpl, Gerald; Shapa, M; Ferrari, Uta; Hapfelmeier, Gerhard; Bondy, B.; Parsons, C.H.; Gilling, Kate E.; Zieglgänsberger, W.; Holsboer, Florian; Rupprecht, Rainer

doi:10.1055/s-2003-825317

Cited by 3 publications

(4 citation statements)

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“…Second, as all studied AP induced a Lo phase bilayer thickness decrease, their clinical use may be associated with changes in the function of the Lo phase-embedded protein in addition to their D 2 blockade. Recent findings indicating that many AP drugs partition within raft fraction of cell membranes are in accordance with this assumption [22]. Antipsychotic drugs may also modify the transduction sequences located into membrane rafts [2,23].…”

Section: Discussionmentioning

confidence: 61%

Modification of membrane heterogeneity by antipsychotic drugs: An X-ray diffraction comparative study

Tessier

Nuss

Staneva

et al. 2008

Journal of Colloid and Interface Science

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Section: Discussionmentioning

confidence: 61%

Modification of membrane heterogeneity by antipsychotic drugs: An X-ray diffraction comparative study

Tessier

Nuss

Staneva

et al. 2008

Journal of Colloid and Interface Science

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“…One of the most intriguing findings from this mouse model of GLP-1R expression is the colocalization of GLP-1R on GABAergic interneurons-specifically the 5-HT3a receptorexpressing subset-within the caudate putamen and frontal cortex. This ionotropic receptor has previously been reported to play a role in depression-like behaviors (Bhatnagar et al, 2004;Eisensamer et al, 2003;Rajkumar & Mahesh, 2010), although it is not clear which region or pool of receptors is responsible for this effect. GLP-1R has been demonstrated to play an intermediary role on GABAergic transmission in in vitro models of febrile seizure (Y.…”

Section: Discussionmentioning

confidence: 99%

A novel mouse model of glucagon‐like peptide‐1 receptor expression: A look at the brain

Graham

Durai

Trammell

et al. 2020

J of Comparative Neurology

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Glucagon-like peptide-1 (GLP-1) is an incretin hormone with a number of functions to maintain energy homeostasis and contribute to motivated behavior, both peripherally and within the central nervous system (CNS). These functions, which include insulin secretion, gastric emptying, satiety, and the hedonic aspects of food and drug intake, are primarily mediated through stimulation of the GLP-1 receptor. While this receptor plays an important role in a variety of physiological outcomes, data regarding its CNS expression has been primarily limited to regional receptor binding and single-label transcript expression studies. We thus developed a bacterial artificial chromosome transgenic mouse, in which expression of a red fluorescent protein (mApple) is driven by the GLP-1R promoter. Using this reporter mouse, we characterized the regional and cellular expression patterns of GLP-1R expressing cells in the CNS, using double-label immunohistochemistry and in situ hybridization. GLP-1R-expressing cells were enriched in several key brain regions and circuits, including the lateral septum, hypothalamus, amygdala, bed nucleus of the stria terminalis, hippocampus, ventral midbrain, periaqueductal gray and cerebral cortex. In most regions, GLP-1R primarily colocalized with GABAergic neurons, except within some regions such as the hippocampus, where it was co-expressed in glutamatergic neurons. GLP-1R-mApple cells were highly co-expressed with 5-HT3 receptor-containing neurons within the cortex and striatum, as well as with dopamine receptor-and calbindin-expressing cells within the lateral septum, the brain region in which GLP-1R is most highly expressed. In this manuscript, we provide detailed images of GLP-1R-mApple expression and distribution within the brain and characterization of these neurons.

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“…Serotonin receptors have been shown to be activated by and accumulate in lipid raft domains (3)(4)(5). Therefore, for maximum bioefficiency it would clearly be advantageous for a drug to accumulate in the same domain as its target.…”

Section: Discussionmentioning

confidence: 99%

“…Cholesterol-rich microdomains ("lipid rafts") add another layer of complexity because the lateral organization of the membrane could well affect the concentration of a drug close to its target protein. This possibility is backed up by the observation that many chemicals, including drugs that target serotonin receptors, preferentially localize into these domains (3)(4)(5). Meanwhile, the location and activity of some membrane proteins, particularly G-protein-coupled receptors, seem to be affected by domains (6).…”

mentioning

confidence: 99%

Cholesterol and Lipid Phases Influence the Interactions between Serotonin Receptor Agonists and Lipid Bilayers

Batchelor

Windle

Buchoux

et al. 2010

Journal of Biological Chemistry

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Solid state NMR techniques have been used to investigate the effect that two serotonin receptor 1a agonists (quipazine and LY-165,163) have on the phase behavior of, and interactions within, cholesterol/phosphocholine lipid bilayers. The presence of agonist, and particularly LY-165,163, appears to widen the phase transitions, an effect that is much more pronounced in the presence of cholesterol. It was found that both agonists locate close to the cholesterol, and their interactions with the lipids are modulated by the lipid phases. As the membrane condenses into mixed liquid-ordered/disordered phases, quipazine is pushed up toward the surface of the bilayer, whereas LY-165,163 moves deeper into the lipid chain region. In light of our results, we discuss the role of lipid/drug interactions on drug efficacy.The majority of drug targets are membrane proteins. Hence the interaction of a drug with the membrane is crucial for its efficacy. A high location probability in a particular part of a membrane and its orientation with respect to the membrane normal could well be relevant to how the drug is presented to the target protein's binding site (1, 2). Cholesterol-rich microdomains ("lipid rafts") add another layer of complexity because the lateral organization of the membrane could well affect the concentration of a drug close to its target protein. This possibility is backed up by the observation that many chemicals, including drugs that target serotonin receptors, preferentially localize into these domains (3-5). Meanwhile, the location and activity of some membrane proteins, particularly G-protein-coupled receptors, seem to be affected by domains (6). Therefore, it is easy to imagine that a drug's efficacy may be limited by it partitioning into a different membrane domain than its target receptor. Furthermore, it is clear that many membrane proteins are modulated by the properties of the surrounding lipids. Hence, a drug has the potential to regulate a protein by altering these properties (7). This raises the intriguing possibility of a class of drugs that, instead of directly targeting a protein, target the membrane in which the protein resides. This route of action was first proposed as early as 1899 as a possible mechanism for general anesthetics, when it was noted that the potency of an anesthetic correlated very strongly with olive oil/water partitioning (8), yet drugs affecting membrane proteins via lipid interactions, so called "membrane-lipid therapy," have only relatively recently been explored (7, 9, 10).Some simple lipid mixtures have been used as models for in vivo microdomains. A particularly well studied mixture consists of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) Proton NMR and specifically magic angle spinning-assisted nuclear Overhauser enhancement spectroscopy (MAS-NOESY) experiments have proven to be an excellent tool for investigating, with atomic resolution, the location of small molecules embedded in lipid membranes (17)(18)(19)(20). However, these studies have been limited to binary...

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Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor

Cited by 3 publications

References 0 publications

Modification of membrane heterogeneity by antipsychotic drugs: An X-ray diffraction comparative study

Modification of membrane heterogeneity by antipsychotic drugs: An X-ray diffraction comparative study

A novel mouse model of glucagon‐like peptide‐1 receptor expression: A look at the brain

Cholesterol and Lipid Phases Influence the Interactions between Serotonin Receptor Agonists and Lipid Bilayers

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