Autoradiographic mapping of the opioid receptor-like 1 (ORL1) receptor in the brains of the mu-, delta-, kappa- opioid receptor knockout mice
Autor: | Robin James Goody, S Clarke, Roberta Lattanzi, Frédéric Simonin, Ian Kitchen, Dominique Filliol, Susan Slowe, Lucia Negri, Brigitte L. Kieffer, Isabelle Lena, Hans W. D. Matthes |
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Jazyk: | angličtina |
Rok vydání: | 2001 |
Předmět: |
Male
medicine.medical_specialty medicine.drug_class Receptors Opioid mu Down-Regulation Pain ORL1 receptor opioid receptors knockout mice autoradiography transgenic Tritium Nociceptin Receptor δ-opioid receptor chemistry.chemical_compound Mice Radioligand Assay Opioid receptor Reference Values Internal medicine Receptors Opioid delta medicine Animals Receptor Insulin-like growth factor 1 receptor Mice Knockout Brain Mapping Chemistry General Neuroscience Receptors Opioid kappa Brain Up-Regulation DAMGO Nociceptin receptor Endocrinology Opioid Opioid Peptides Knockout mouse Receptors Opioid Female medicine.drug |
Popis: | The opioid receptor-like 1 (ORL1) receptor shares a high degree of sequence homology with the classical mu-, delta- and kappa-opioid receptors and a functional mutual opposition between these receptors has been suggested. To further address this possible interaction we have used mu-, delta- and kappa-opioid receptor knockout mice to determine autoradiographically if there are any changes in the number or distribution of the ORL1 receptor, labelled with [(3)H]nociceptin, in the brains of mice deficient in each of the opioid receptors. An up-regulation of ORL1 expression was observed across all brain regions in delta-knockouts with cortical regions typically showing a 15-30% increase in binding that was most marked in heterozygous mice. In contrast, ORL1 receptor expression was down-regulated in virtually all brain structures in heterozygous kappa-knockouts although the magnitude of this change was not as great as for the delta-knockouts. No significant alterations in ORL1 receptor expression were observed across brain regions in mu-receptor knockout mice and there were no qualitative differences in ORL1 receptor expression in any groups. These data suggest there are interactions between the ORL1 system and the classical opioid receptors and that the interactions are receptor-specific. The greater differences observed in heterozygous mice suggest that these interactions might be most relevant when there is only partial loss of receptor function. |
Databáze: | OpenAIRE |
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