Adenosine: A partial agonist of the growth hormone secretagogue receptor
| Autor: | Denis Leong, Reid J. Leonard, Roy G. Smith, Kang Cheng, Anna Pomés, Patrick R. Griffin, James M. Schaeffer, Alexander G.A. Smith, Jimmy Calacay, Ken Liu, Lex H.T. Van der Ploeg, Scott D. Feighner, C.-S. Pong, Yuan Xu, Andrew D. Howard |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cell Extracts
Adenosine Indoles Swine Dopamine Growth hormone secretagogue receptor Biophysics Hypothalamus Receptors Cell Surface Adenosine-5'-(N-ethylcarboxamide) Pharmacology Ligands Biochemistry Partial agonist Models Biological Mass Spectrometry Cell Line Receptors G-Protein-Coupled Adenosine A1 receptor Aequorin Theophylline medicine Animals Humans Spiro Compounds Binding site Receptors Ghrelin Molecular Biology Chromatography High Pressure Liquid Neurons Binding Sites Chemistry Cell Biology Purinergic signalling Ligand (biochemistry) Luminescent Measurements Mutagenesis Site-Directed hormones hormone substitutes and hormone antagonists Adenosine A2B receptor medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 276(3) |
| ISSN: | 0006-291X |
| Popis: | The growth hormone secretagogue receptor (GHS-R) is involved in the regulation of pulsatile GH release. However, until recently, natural endogenous ligands for the receptor were unknown. We fractionated porcine hypothalamic extracts and assayed fractions for activity on HEK293 cells expressing GHS-R and aequorin. A partial agonist was isolated and identified using microspray tandem mass spectrometry as adenosine. GHS-R activation by adenosine and synthetic adenosine agonists is inhibited by the GHS-R selective antagonists L-765,867, D-Lys 3 -GHRP-6, and by theophylline and XAC. Cross desensitization of the GHS-R occurs with both MK-0677 and adenosine. Ligand binding and site directed mutagenesis studies show that adenosine binds to a binding site that is distinct from the previously characterized MK-0677 and GHRP-6 binding pocket. We propose, that adenosine is a physiologically important endogenous GHS-R ligand and speculate that GHS-R ligands modulate dopamine release from hypothalamic neurons. |
| Databáze: | OpenAIRE |
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