Molecular Biology and Genomic Organization of G Protein-Coupled Serotonin Receptors

2008 ◽  
pp. 1-38 ◽  
Author(s):  
Wesley K. Kroeze ◽  
Bryan L. Roth
Keyword(s):  
Molecular Biology ◽  
G Protein ◽  
Serotonin Receptors ◽  
Genomic Organization ◽  
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.

G protein-coupled P2 purinoceptors: from molecular biology to functional responses

1995 ◽  
Vol 16 (4) ◽  
pp. 133-139 ◽  
Author(s):  
M.R. Boarder ◽  
G.A. Weisman ◽  
J.T. Turner ◽  
G.F. Wilkinson
Keyword(s):  
Molecular Biology ◽  
G Protein ◽  
Functional Responses ◽  
P2 Purinoceptors ◽  
G Protein Coupled

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.

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