Ghrelin and des-acyl ghrelin both inhibit isoproterenol-induced lipolysis in rat adipocytes via a non-type 1a growth hormone secretagogue receptor
| Autor: | Riccarda Granata, Ezio Ghigo, Nicoletta Pons, Filomena Catapano, Giampiero Muccioli, Corrado Ghè |
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| Rok vydání: | 2004 |
| Předmět: |
Agonist
Glycerol Male medicine.medical_specialty Indoles medicine.drug_class Lipolysis Peptide Hormones Growth hormone secretagogue receptor Adipose tissue Gene Expression Binding Competitive Receptors G-Protein-Coupled chemistry.chemical_compound Internal medicine Adipocyte Receptors Adrenergic beta medicine Adipocytes Animals Spiro Compounds RNA Messenger Rats Wistar Receptor Growth Substances Receptors Ghrelin Cells Cultured Pharmacology Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction digestive oral and skin physiology Isoproterenol Ghrelin Rats Somatropin Endocrinology chemistry Adipose Tissue Oligopeptides hormones hormone substitutes and hormone antagonists |
| Zdroj: | European journal of pharmacology. 498(1-3) |
| ISSN: | 0014-2999 |
| Popis: | Besides possessing a strong growth hormone (GH)-releasing activity, the gastrointestinal octanoylated peptide ghrelin has been reported to antagonize lipolysis in rat adipocytes. It is not yet clear whether this inhibitory activity on lipolysis is also shared by the major circulating isoform, des-acyl ghrelin, that does not activate the ghrelin receptor, namely the type 1a GH secretagogue-receptor (GHS-R1a) and lacks the endocrine effects of the acylated form. Here we show that des-acyl ghrelin, like ghrelin and some synthetic GHS (hexarelin and MK0677) and carboxy-terminally ghrelin fragments such as ghrelin-(1-5) and ghrelin-(1-10), all significantly reduced, over concentrations ranging from 1 to 1000 nM, the stimulation of glycerol release caused in rat epididymal adipocytes by the nonselective β-adrenoceptor agonist isoproterenol in vitro. The order of potency on stimulated-lipolysis was: des-acyl ghrelin=ghrelin>MK0677=hexarelin>ghrelin-(1-5)=ghrelin-(1-10). This ranking was consistent with the binding experiments performed on membranes of epididymal adipose tissue or isolated adipocytes that did not express mRNA for GHS-R1a. A common high-affinity binding site was recognized in these cells by both acylated and des-acylated ghrelin and also by hexarelin, MK0677, ghrelin-(1-5) and ghrelin-(1-10). In conclusion, these findings provide the first evidence that des-acyl ghrelin, as well as ghrelin, short ghrelin fragments and synthetic GHS, may act directly as antilipolytic factors on the adipose tissue through binding to a specific receptor which is distinct from GHS-R1a. |
| Databáze: | OpenAIRE |
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