ArticleMolecular pharmacology2009
Growth hormone secretagogues and growth hormone releasing peptides act as orthosteric super-agonists but not allosteric regulators for activation of the G protein Galpha(o1) by the Ghrelin receptor.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways.Acta pharmacologica Sinica · 2022Article
- Encoding the β-Arrestin Trafficking Fate of Ghrelin Receptor GHSR1a: C-Tail-Independent Molecular Determinants in GPCRs.ACS pharmacology & translational science · 2019Article
- Discovery of a GPR40 Superagonist: The Impact of Aryl Propionic Acid α-Fluorination.ACS medicinal chemistry letters · 2019Article
- Ghrelin Aggravates Prostate Enlargement in Rats with Testosterone-Induced Benign Prostatic Hyperplasia, Stromal Cell Proliferation, and Smooth Muscle Contraction in Human Prostate Tissues.Oxidative medicine and cellular longevity · 2019Article
- Translating biased signaling in the ghrelin receptor system into differential in vivo functions.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer's Disease.International journal of molecular sciences · 2018Article
- Clarifying the Ghrelin System's Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand.International journal of molecular sciences · 2017Review
- Therapeutic Potential of Targeting the Ghrelin Pathway.International journal of molecular sciences · 2017Review
- Superagonism at G protein-coupled receptors and beyond.British journal of pharmacology · 2016Review
- A Significant Role of the Truncated Ghrelin Receptor GHS-R1b in Ghrelin-induced Signaling in Neurons.The Journal of biological chemistry · 2016Article
- Agonism, Antagonism, and Inverse Agonism Bias at the Ghrelin Receptor Signaling.The Journal of biological chemistry · 2015Article
- The β-cell GHSR and downstream cAMP/TRPM2 signaling account for insulinostatic and glycemic effects of ghrelin.Scientific reports · 2015Article
- Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons.The Journal of general physiology · 2015Article
- G Protein and β-arrestin signaling bias at the ghrelin receptor.The Journal of biological chemistry · 2014Article
- Functionally biased signalling properties of 7TM receptors - opportunities for drug development for the ghrelin receptor.British journal of pharmacology · 2013Review
- Anti-ghrelin immunoglobulins modulate ghrelin stability and its orexigenic effect in obese mice and humans.Nature communications · 2013Article
- Oligoclonal antibody targeting ghrelin increases energy expenditure and reduces food intake in fasted mice.Molecular pharmaceutics · 2012Article
- High constitutive activity is an intrinsic feature of ghrelin receptor protein: a study with a functional monomeric GHS-R1a receptor reconstituted in lipid discs.The Journal of biological chemistry · 2012Article
- Heteromultimerization of cannabinoid CB(1) receptor and orexin OX(1) receptor generates a unique complex in which both protomers are regulated by orexin A.The Journal of biological chemistry · 2011Article
- Integrating GHS into the Ghrelin System.International journal of peptides · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Some growth hormone secretagogues act as agonists at the ghrelin receptor and have been described as "ago-allosteric" ligands because of an ability to also modulate the maximum efficacy and potency of ghrelin (Holst et al., 2005). In membranes prepared from cells coexpressing the human ghrelin receptor and the G protein Galpha(o1), N-[1(R)-1, 2-dihydro-1-ethanesulfonylspiro-3H-indole-3,4'-piperidin)-1'-yl]carbonyl-2-(phenylmethoxy)-ethyl-2-amino-2-methylpropanamide (MK-677), growth hormone-releasing peptide 6 (GHRP-6), and the 2(R)-hydroxypropyl derivative of 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5-yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamide (L-692,585) each functioned as direct agonists, and each displayed higher efficacy than ghrelin. The effect of multiple, fixed concentrations of each of these ligands on the function and concentration-dependence of ghrelin and the effect of multiple, fixed concentrations of ghrelin on the action of MK-677, GHRP-6, and L-692,585 was analyzed globally according to a modified version of an operational model of allosterism that accounts for allosteric modulation of affinity, efficacy, and allosteric agonism. Each of the data sets was best fit by a model of simple competition between a partial and a full agonist. Both positive and negative allosteric modulators are anticipated to alter the kinetics of binding of an orthosteric agonist. However, none of the proposed ago-allosteric regulators tested had any effect on the dissociation kinetics of (125)I-[His]-ghrelin, and GHRP-6 and MK-677 were able to fully displace (125)I-[His]-ghrelin from the receptor. At least in the system tested, each of the ligands acted in a simple competitive fashion with ghrelin as demonstrated by analysis according to a model whereby ghrelin is a partial agonist with respect to each of the synthetic agonists tested.
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