title: Distribution of ORL-1 receptor binding and receptor-activated G-proteins in rat forebrain and their experimental localization in anterior cingulate cortex.
abstract: Opioid receptor-like (ORL-1) receptors and ORL-1-activated G-proteins are found in high levels in the forebrain, particularly cingulate cortex, an area involved in processing of nociceptive stimuli. [(3)H]nociceptin/orphanin FQ (N/OFQ) and N/OFQ-stimulated [(35)S]GTPgammaS autoradiography in rat brain were used to localize ORL-1 receptors and activated G-proteins, respectively. N/OFQ binding and activated G-proteins were highest in anterior cingulate, agranular insula, piriform, perirhinal and entorhinal cortices; midline and intralaminar thalamic nuclei; and subnuclei of the amygdala and hippocampus. In anterior cingulate area 24, [(3)H]N/OFQ and N/OFQ-stimulated [(35)S]GTPgammaS binding were highest in layers V and VI. The cellular localization of ORL-1 receptors and activated G-proteins in area 24 was examined using two strategies: ibotenic acid injection into the cortex or undercut lesions to remove afferent axons, followed by autoradiography. Ibotenic acid lesions that destroyed neurons in the anterior cingulate cortex decreased [(3)H]N/OFQ binding by 75-80% and reduced N/OFQ-stimulated [(35)S]GTPgammaS binding to basal levels seen in the absence of agonist. Deafferentation lesions increased [(3)H]N/OFQ binding by 40-50%, with no significant change in N/OFQ-stimulated [(35)S]GTPgammaS binding. These data demonstrate that ORL-1 receptors in layer V of anterior cingulate cortex are located on somatodendritic elements and that deafferentation increases ORL-1 receptor binding.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University Medical College of Virginia, Richmond, VA 23298, USA. ljsimsel@hsc.vcu.edu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Sim-Selley
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Vogt
authors.forename: Steven R
authors.initials: SR
authors.lastname: Childers
authors.forename: Brent A
authors.initials: BA
authors.lastname: Vogt
mesh_terms: D000818:Animals; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D016548:Prosencephalon / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D011957:Receptors, Opioid / Q000032:analysis / Q000378:metabolism*; D000094942:Nociceptin Receptor
chemical_list: D019204:GTP-Binding Proteins; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722285:Oprl1 protein, rat