Comparison between delta-opioid receptor functional response and autoradiographic labeling in rat brain and spinal cord.
The distribution of delta-opioid receptors (DORs) in the rat central nervous system has been previously characterized by radioligand binding and immunohistochemistry. However, the functional neuroanatomy of DORs has not been mapped in any detail; this is potentially important, because these receptors appear to be primarily cytosolic. Opioid receptors can couple to G(i/o) G proteins, a process that is detected by agonist-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate ([35S]GTPgammaS) binding. The purpose of this study was therefore to determine the distribution of functional DORs, as assessed by [35S]GTPgammaS autoradiographic labeling in response to the DOR agonist deltorphin II. For comparison, adjacent sections were labeled with [125I]deltorphin II or the DOR antagonist [125I]AR-M100613. In all three assays, mu-opioid receptors were blocked pharmacologically. The distributions of [125I]deltorphin II and [125I]AR-M100613 were highly correlated but not identical. Deltorphin II increased [35S]GTPgammaS binding in a concentration-dependent and naltrindole-sensitive manner. The regional [35S]GTPgammaS response to deltorphin II was only moderately predicted by agonist or antagonist radioligand binding (r = 0.67 and 0.50, respectively). [35S]GTPgammaS responses to deltorphin II were strongest in the extended striatum (caudate putamen, nucleus accumbens, olfactory tubercle) and cerebral cortex. In contrast, some areas reported to mediate DOR analgesia (brainstem, spinal cord) possessed a much lower [35S]GTPgammaS response. These findings demonstrate the existence of a partial mismatch between DOR radioligand binding and [35S]GTPgammaS response. This divergence possibly reflects regional heterogeneity in G-protein receptor coupling, or in the subcellular localization of DOR.
Pradhan
Amynah Amir Ali
AA
Department of Pharmacology and Therapeutics, McGill University, Montreal QC H3G 1Y6, Canada.
Clarke
Paul Brian Sydenham
PB
D000698:Analgesia; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009842:Oligopeptides / Q000378:metabolism; D010146:Pain / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D014018:Tissue Distribution
D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C060209:deltorphin II, Ala(2)-