Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells
| Autor: | Daniel Caput, Pascual Ferrara, Pascale Chalon, Andre Bachy, Marie Guillemot, Gérard Le Fur, Stéphanie Garcia, Caroline Poinot-Chazel, Natalio Vita, P. Casellas, Olivier Thurneyssen, Jean Pierre Maffrand, Mourad Kaghad, P.E. Keane, F. Oury-Donat, Philippe Soubrie |
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| Rok vydání: | 1998 |
| Předmět: |
Agonist
medicine.medical_specialty DNA Complementary medicine.drug_class Molecular Sequence Data Histamine H1 receptor CHO Cells Biology Pharmacology Xenin complex mixtures chemistry.chemical_compound Internal medicine Cricetinae Enzyme-linked receptor medicine Animals Humans Receptors Neurotensin Tissue Distribution Amino Acid Sequence RNA Messenger Cloning Molecular Receptor Neurotensin Sequence Homology Amino Acid musculoskeletal neural and ocular physiology digestive oral and skin physiology Levocabastine Recombinant Proteins Endocrinology nervous system chemistry Neuromedin N hormones hormone substitutes and hormone antagonists medicine.drug Signal Transduction |
| Zdroj: | European journal of pharmacology. 360(2-3) |
| ISSN: | 0014-2999 |
| Popis: | The human levocabastine-sensitive neurotensin NT2 receptor was cloned from a cortex cDNA library and stably expressed in Chinese hamster ovary (CHO) cells in order to study its binding and signalling characteristics. The receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. It also binds levocabastine, a histamine H1 receptor antagonist that is not recognised by neurotensin NT1 receptor. Neurotensin binding to recombinant neurotensin NT2 receptor expressed in CHO cells does not elicit a biological response as determined by second messenger measurements. Levocabastine, and the peptides neuromedin N and xenin were also ineffective on neurotensin NT2 receptor activation. Experiments with the neurotensin NT1 receptor antagonists SR48692 and SR142948A, resulted in the unanticipated discovery that both molecules are potent agonists on neurotensin NT2 receptor. Both compounds, following binding to neurotensin NT2 receptor, enhance inositol phosphates (IP) formation with a subsequent [Ca2+]i mobilisation; induce arachidonic acid release; and stimulate mitogen-activated protein kinase (MAPK) activity. Interestingly, these activities are antagonised by neurotensin and levocabastine in a concentration-dependent manner. These activities suggest that the human neurotensin NT2 receptor may be of physiological importance and that a natural agonist for the receptor may exist. |
| Databáze: | OpenAIRE |
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