scholarly journals Specificity and nanomolar potency of melatonin on G-protein coupled melatonin MT1 and MT2 receptors expressed in HEK-293T human embryo kidney cells

2019 ◽  
Vol 2 (4) ◽  
pp. 121-131 ◽  
Author(s):  
Rafael Rivas-Santisteban ◽  
Irene Reyes-Resina ◽  
Iu Raich ◽  
Jesus J Pintor ◽  
Hanan Awad Alkozi ◽  
...  
Keyword(s):  
G Protein ◽  
Standard Procedure ◽  
G Protein Coupled Receptors ◽  
Prolonged Release ◽  
Therapeutic Effects ◽  
Selective Agonist ◽  
Human Embryo Kidney ◽  
G Protein Coupled ◽  
Camp Levels ◽  
Nanomolar Range

This is a pre-registered study, i.e. a study whose hypotheses and experiments designed to address these hypotheses have been deposited in a database before starting the experiments. The study aims at assessing the Gs versus Gi coupling and the potency of melatonin in the human version of melatonin MT1 and MT2 G-protein-coupled receptors expressed in HEK-293T cells. The results show that these receptors are Gi but not Gs coupled. By using a standard procedure of modulation of 0.5 µM forskolin-induced cAMP levels, it was found that the potency on MT2 receptor-mediated actions is in the low nanomolar range, but the potency on MT1 receptor is in the high nanomolar range.  The potency of melatonin to stimulate the MT2 receptor is similar to that of a selective agonist, N-[2-(2-methoxy-6H-isoindolo[2,1-a]indol-11-yl)ethyl]butanamide (IIK7). Overall, the data on the potency of melatonin on its receptors will provide a new look for melatonin research. It is important to consider this finding for appropriately addressing physiological or therapeutic effects based on melatonin potency. Thus, the low doses of melatonin used in the existing prolonged release preparations or in other supplements should be revisited.  

G-protein coupled receptor auto-antibodies in thromboangiitis obliterans (Buerger’s disease) and their removal by immunoadsorption

VASA ◽  
2014 ◽  
Vol 43 (5) ◽  
pp. 347-352 ◽  
Author(s):  
Peter F. Klein-Weigel ◽  
Marion Bimmler ◽  
Petra Hempel ◽  
Sebastian Schöpp ◽  
Siegrid Dreusicke ◽  
...  
Keyword(s):  
G Protein ◽  
Adrenergic Receptor ◽  
G Protein Coupled Receptors ◽  
Thromboangiitis Obliterans ◽  
Therapeutic Effects ◽  
Study Group ◽  
Eta Receptor ◽  
Serological Data ◽  
Agonistic Autoantibodies ◽  
G Protein Coupled

Background: Immunhistopathological and serological data favors an immunopathogenesis of thromboangiitis onliterans(TAO, Buerger’s disease). Autoantbodies seem to play a major role. Immunoadsorption (IA) proved to be therapeutically effective. We focused on agonistic autoantibodies (agAAB) directed against G-protein coupled receptors (GPCR) and proved the hypothesis, that these agAAB might be present in TAO and that a five day course of IA might be able to eliminate these agAAB effectively. Patients and methods: Between December 2012 and May 2014 11 TAO-patients were treated by IA in a five day course. AgAAB-analysis was performed using specific ELISA techniques. Results: AgAAB were detected in 9 out of 11 patients (81.8 %).Multiple agAAB were present in 7 patients (63.6 %). A clustering of agAAB directed against loop1 of the adrenergic α1-receptor and the endothelin-A-(ETA)receptor was identified, representing 72.7 % resp. 54.5 % of the patients. AgAAB directed against the angiotensin-1 (AT-1) epitope 1 or 2 were detected in 3 patients and agAAB directed against protease-activated receptor (PAR) loop1/2 were seen in 2 patients. AgAAB directed against ETA-receptor loop1 never appeared without agAAB directed against α1-receptor loop1. Immediately after a five day-course of IA agAAB were absent in 81.8 % of the total study group and in 77.8 % of all cases tested positive for agAAB before IA. Conclusions: AgAAB directed against GPCR were identified in TAO patients with a clustering of agAAB directed against α-1-adrenergic receptor loop1 and ETA-receptor loop1. AgAA were eliminated by IA in the majority of cases. We suggest that these agAA play an important role in the pathogenesis of TAO and that their elimination might be responsible for the positive therapeutic effects reported in patients treated with IA.

scholarly journals Extensive crosstalk of G protein-coupled receptors with the Hedgehog signalling pathway

Development ◽  
2021 ◽  
pp. dev.189258
Author(s):  
Farah Saad ◽  
David R. Hipfner
Keyword(s):  
G Protein ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
G Protein Coupled Receptors ◽  
Signalling Pathway ◽  
Protein Activity ◽  
Cellular Sensitivity ◽  
Hedgehog Signalling Pathway ◽  
G Protein Coupled ◽  
Camp Levels

Hedgehog (Hh) ligands orchestrate tissue patterning and growth by acting as morphogens, dictating different cellular responses depending on ligand concentration. Cellular sensitivity to Hh ligands is influenced by heterotrimeric G protein activity, which controls production of the second messenger 3',5'-cyclic adenosine monophosphate (cAMP). cAMP in turn activates Protein kinase A (PKA), which functions as an inhibitor and (uniquely in Drosophila) an activator of Hh signalling. A few mammalian Gαi- and Gαs-coupled G protein-coupled receptors (GPCRs) have been shown to influence Sonic Hh (Shh) responses in this way. To determine if this is a more general phenomenon, we carried out an RNAi screen targeting GPCRs in Drosophila. RNAi-mediated depletion of more than 40% of GPCRs tested either decreased or increased Hh responsiveness in the developing Drosophila wing, closely matching the effects of Gαs and Gαi depletion, respectively. Genetic analysis indicated that the orphan GPCR Mthl5 lowers cAMP levels to attenuate Hh responsiveness. Our results identify Mthl5 as a new Hh signalling pathway modulator in Drosophila and suggest that many GPCRs may crosstalk with the Hh pathway in mammals.

scholarly journals Metabolic Functions of G Protein-Coupled Receptors in Hepatocytes—Potential Applications for Diabetes and NAFLD

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1445
Author(s):  
Takefumi Kimura ◽  
Sai P. Pydi ◽  
Jonathan Pham ◽  
Naoki Tanaka
Keyword(s):  
G Protein ◽  
Metabolic Diseases ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Therapeutic Effects ◽  
Nonalcoholic Fatty Liver ◽  
Therapeutic Implications ◽  
Surface Receptors ◽  
Metabolic Role ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) are cell surface receptors that mediate the function of extracellular ligands. Understanding how GPCRs work at the molecular level has important therapeutic implications, as 30–40% of the drugs currently in clinical use mediate therapeutic effects by acting on GPCRs. Like many other cell types, liver function is regulated by GPCRs. More than 50 different GPCRs are predicted to be expressed in the mouse liver. However, knowledge of how GPCRs regulate liver metabolism is limited. A better understanding of the metabolic role of GPCRs in hepatocytes, the dominant constituent cells of the liver, could lead to the development of novel drugs that are clinically useful for the treatment of various metabolic diseases, including type 2 diabetes, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In this review, we describe the functions of multiple GPCRs expressed in hepatocytes and their role in metabolic processes.

Sign in / Sign up

Export Citation Format

Share Document