Autoradiography of opioid and ORL1 ligands in opioid receptor triple knockout mice - PubMed (original) (raw)
Comparative Study
. 2002 Nov;16(9):1705-12.
doi: 10.1046/j.1460-9568.2002.02239.x.
Traci Czyzyk, Micheal Ansonoff, Joshua F Nitsche, Ming-Sing Hsu, Linda Nilsson, Kerstin Larsson, Anna Borsodi, Geza Toth, Ray Hill, Ian Kitchen, John E Pintar
Affiliations
- PMID: 12431223
- DOI: 10.1046/j.1460-9568.2002.02239.x
Comparative Study
Autoradiography of opioid and ORL1 ligands in opioid receptor triple knockout mice
Siân Clarke et al. Eur J Neurosci. 2002 Nov.
Abstract
Three genes for the opioid receptors ( micro, delta and kappa) and a gene coding for a related receptor (ORL1) have been cloned but pharmacological studies suggest that further subtypes exist that remain poorly understood. To determine if there are other classically defined opioid binding sites we have carried out homogenate binding and section autoradiography with [3H]naloxone in mice that lack all three opioid genes and are hyperalgesic in a thermal nociceptive test. We have also examined [3H]bremazocine labelling in triple knockout brain and spinal cord as this ligand has been proposed to label novel kappa-receptors. No receptor labelling for either ligand was detected in the brains or spinal cord of knockout mice demonstrating that all binding is the product of the three known receptors and that there is no cross-labelling of the ORL1 receptor. Nociceptin (1 micro m) caused marked displacement of [3H]bremazocine in wild-type brains indicating that nociceptin at high concentrations can displace classical opioid binding. As a number of studies have proposed a close association between the classical opioid receptors and the ORL1 system we also hypothesized that loss of all of the classical opioid receptors might lead to compensatory changes in ORL1 receptors. Labelling of the ORL1 receptor with [3H]nociceptin showed region-dependent quantitative increases in triple knockout brains indicating a close relationship between the two systems in specific brain areas.
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