Autoradiography in opioid triple knockout mice reveals opioid and opioid receptor like binding of naloxone benzoylhydrazone
| Autor: | John E. Pintar, Siân Clarke, Veronica Cox, Ming Sing Hsu, Csaba Tömböly, Anna Borsodi, Tracy Czyzyk, Ian Kitchen, Géza Tóth, Joshua F. Nitsche, Micheal Ansonoff, Raymond G. Hill |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Receptors Opioid mu Pharmacology Cellular and Molecular Neuroscience Mice Opioid receptor Labelling Opioid Receptor Binding Internal medicine Receptors Opioid delta medicine Animals Receptor Mice Knockout Chemistry Naloxone Receptors Opioid kappa Brain Nociceptin receptor Endocrinology Opioid Knockout mouse Autoradiography Diprenorphine medicine.drug Protein Binding |
| Zdroj: | Neuropharmacology. 48(2) |
| ISSN: | 0028-3908 |
| Popis: | Naloxone benzoylhydrazone (NalBzoH) is a ligand used to study opioid receptors. It has been suggested to act at a novel kappa3 receptor but also appears to bind to classical opioid receptors, and possibly the ORL1 receptor. We have used opioid receptor triple knockout mice, deficient in genes coding for the mu, delta and kappa-receptor, to characterise the relative contributions of opioid and ORL1 activity to the binding of this ligand, by carrying out receptor autoradiography with [3H]NalBzoH. As competing ligands we have used diprenorphine and nociceptin at 1 microM, alone or in combination, to determine the contribution of opioid and ORL1 receptor binding. At 4 nM [3H]NalBzoH showed labelling in wild-type brains indicative of broad spectrum classical opioid receptor binding. In the triple knockout brains all labelling was completely absent, suggesting that at this concentration there is no binding to ORL1 sites. However at 50 nM [3H]NalBzoH showed labelling in triple knockout brains with a distribution pattern indicative of ORL1 labelling. Quantitative analysis showed that nociceptin displaced typically 30% of the residual labelling in knockout brains whilst diprenorphine had relatively little effect. The data show that at 50 nM NalBzoH no binding was detected other than to classical opioid receptors or to ORL1 in an approximate ratio of 2:1. |
| Databáze: | OpenAIRE |
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