MilliporeSigma
  • Home
  • Search Results
  • Ghrelin's Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction.

Ghrelin's Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction.

ACS chemical neuroscience (2015-03-03)
Harriët Schellekens, Pablo N De Francesco, Dalia Kandil, Wessel F Theeuwes, Triona McCarthy, Wesley E P A van Oeffelen, Mario Perelló, Linda Giblin, Timothy G Dinan, John F Cryan
ABSTRACT

Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghrelin's orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghrelin's orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management.

MATERIALS
Product Number
Brand
Product Description

SAFC
HEPES
Sigma-Aldrich
Hydrochloric acid solution, 32 wt. % in H2O, FCC
Sigma-Aldrich
Cytosine, ≥99%
Sigma-Aldrich
Hydrocortisone, meets USP testing specifications
Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
Sigma-Aldrich
Hydrocortisone, ≥98% (HPLC)
Sigma-Aldrich
Hexadimethrine bromide, ≥94% (titration)
Sigma-Aldrich
Hydrocortisone, γ-irradiated, powder, BioXtra, suitable for cell culture
Supelco
Hydrochloric acid solution, volumetric, 0.1 M HCl (0.1N), endotoxin free
Sigma-Aldrich
Hydrochloric acid solution, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
HEPES, BioXtra, pH 5.0-6.5 (1 M in H2O), ≥99.5% (titration)
Sigma-Aldrich
HEPES, BioPerformance Certified, ≥99.5% (titration), suitable for cell culture
Sigma-Aldrich
HEPES, BioXtra, suitable for mouse embryo cell culture, ≥99.5% (titration)
Sigma-Aldrich
HEPES, ≥99.5% (titration)
Sigma-Aldrich
Hydrochloric acid solution, ~6 M in H2O, for amino acid analysis
Sigma-Aldrich
HEPES buffer solution, 1 M in H2O
Sigma-Aldrich
Hydrochloric acid, 36.5-38.0%, BioReagent, for molecular biology
Sigma-Aldrich
Poly-L-lysine solution, 0.1 % (w/v) in H2O
Sigma-Aldrich
HEPES, BioUltra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
Hydrogen chloride solution, 3 M in cyclopentyl methyl ether (CPME)
Sigma-Aldrich
HEPES, anhydrous, free-flowing, Redi-Dri, ≥99.5%
SAFC
HEPES
Sigma-Aldrich
Adenosine 3′,5′-cyclic monophosphate, ≥98.5% (HPLC), powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology