G protein-coupled serotonin receptors

1996 ◽  
pp. 281-300
Author(s):  
Jean C. Shih ◽  
Timothy K. Gallaher
Keyword(s):  
G Protein ◽  
Serotonin Receptors ◽  
G Protein Coupled

Polypharmacology – a challenge for current drug design approaches

2019 ◽  
Vol 6 (3) ◽  
pp. 19-23
Author(s):  
Sabina Podlewska ◽  
Rafał Kurczab
Keyword(s):  
Molecular Modeling ◽  
Side Effects ◽  
Drug Design ◽  
G Protein ◽  
Design Process ◽  
Serotonin Receptors ◽  
G Protein Coupled Receptors ◽  
Activity Profile ◽  
Activity Groups ◽  
G Protein Coupled

Drug design process faces many challenges, and the most important ones are connected with side effects. Finding compounds that possess affinity towards target of interest is relatively simple; however, an approach one disease-one target is now making space for the search of polypharmacological ligands, where activity towards several proteins is considered at one time. Such proteins are not always the target ones, but very often such panels include also anti-targets, interaction with which is not desired, due to the side effects that may occur upon such contact. In the study, we examined ligands of four G protein-coupled receptors, forming antipsychotic profile: dopamine receptor D2, serotonin receptors 5-HT2A, 5-HT2C (anti-target), and 5-HT6. Number of ligands belonging to particular activity groups, as well as the selected compound structures are examined in detail. Also compound similarity between sets of different activity groups is analysed, giving a picture of difficulty of constructing molecular modeling methodologies that can help in the search of compounds with desired activity profile.

scholarly journals A microbial metabolite synergizes with endogenous serotonin to triggerC. elegansreproductive behavior

2020 ◽  
Vol 117 (48) ◽  
pp. 30589-30598
Author(s):  
Yen-Chih Chen ◽  
Mohammad R. Seyedsayamdost ◽  
Niels Ringstad
Keyword(s):  
Natural Products ◽  
G Protein ◽  
Serotonin Receptors ◽  
Structural Similarity ◽  
Egg Laying ◽  
Microbial Metabolite ◽  
Serotonin Signaling ◽  
Behavior Based ◽  
Small Molecule Therapeutics ◽  
G Protein Coupled

Natural products are a major source of small-molecule therapeutics, including those that target the nervous system. We have used a simple serotonin-dependent behavior of the roundwormCaenorhabditis elegans, egg laying, to perform a behavior-based screen for natural products that affect serotonin signaling. Our screen yielded agonists of G protein-coupled serotonin receptors, protein kinase C agonists, and a microbial metabolite not previously known to interact with serotonin signaling pathways: the disulfide-bridged 2,5-diketopiperazine gliotoxin. Effects of gliotoxin on egg-laying behavior required the G protein-coupled serotonin receptors SER-1 and SER-7, and the Gqortholog EGL-30. Furthermore, mutants lacking serotonergic neurons and mutants that cannot synthesize serotonin were profoundly resistant to gliotoxin. Exogenous serotonin restored their sensitivity to gliotoxin, indicating that this compound synergizes with endogenous serotonin to elicit behavior. These data show that a microbial metabolite with no structural similarity to known serotonergic agonists potentiates an endogenous serotonin signal to affect behavior. Based on this study, we suggest that microbial metabolites are a rich source of functionally novel neuroactive molecules.

Palmitoylation of serotonin receptors

2013 ◽  
Vol 41 (1) ◽  
pp. 89-94 ◽  
Author(s):  
Nataliya Gorinski ◽  
Evgeni Ponimaskin
Keyword(s):  
G Protein ◽  
Serotonin Receptors ◽  
Current Knowledge ◽  
G Protein Coupled Receptors ◽  
Covalent Attachment ◽  
Post Translational Modification ◽  
G Protein Coupling ◽  
Hydroxytryptamine Receptors ◽  
G Protein Coupled ◽  
Multiple Receptor

The covalent attachment of palmitic acid to one or more cysteine residues (S-palmitoylation) is a widespread modification of signalling proteins. With the finding that palmitoylation is a dynamic process, it is now widely accepted that repeated cycles of palmitoylation/depalmitoylation could be involved in the regulation of multiple signalling processes. Palmitoylation also represents a common post-translational modification of the GPCRs (G-protein-coupled receptors). Functionally, palmitoylation of GPCRs has been shown to play a central role in the regulation of multiple receptor functions, including determining the efficiency and selectivity of G-protein coupling, receptor phosphorylation and desensitization, endocytosis and transport to the plasma membrane. The present review summarizes our current knowledge of the palmitoylation of serotonin (5-hydroxytryptamine) receptors and its role in the regulation of receptor functions.

Characterization of the Caenorhabditis elegans G protein-coupled serotonin receptors

2006 ◽  
Vol 6 (4) ◽  
pp. 189-205 ◽  
Author(s):  
Maïté Carre-Pierrat ◽  
David Baillie ◽  
Robert Johnsen ◽  
Rhonda Hyde ◽  
Anne Hart ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
G Protein ◽  
Serotonin Receptors ◽  
G Protein Coupled

A compendium of G-protein–coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure

2020 ◽  
Vol 134 (5) ◽  
pp. 473-512 ◽  
Author(s):  
Ryan P. Ceddia ◽  
Sheila Collins
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Signaling Pathways ◽  
G Protein ◽  
Uncoupling Protein ◽  
Beige Adipocytes ◽  
Nucleotide Regulation ◽  
Ucp1 Expression ◽  
Thermogenic Adipocytes ◽  
G Protein Coupled

Abstract With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand–receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein–coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.

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