Studies of G Protein Activation of Orphanin FQ in the Cerebrum, Thalamus and Spinal Cord of Monkeys

Abstract

Background: The aim of this in vitro study was to investigate []GTPS binding stimulated activation by orphanin FQ in monkey cerebral, thalamic, and spinal membranes. Methods: A rhesus monkey (Macaca mulatta, female, n = 1) was euthanized to obtain cerebral, thalamic, and spinal cord membrane preparations. In the orphanin FQ-stimulated []GTPS binding dose-response curve, (effective concentration 50, nanomolar) and maximum stimulation (% over basal) were determined in the absence or presence of each opioid receptor antagonist, namely, naloxone (20 nM), nor-BNI (3 nM), naltrindole (3 nM), or J-113397 (10 nM) antagonists of the , and nociceptin- opioid receptors respectively. Results: The values of EC50 and maximum stimulation of []GTPS binding were as follows: cortex (5.1 1.4 nM / 55.6 8.2%), thalamus (8.5 [ 1.3 nM / 27.8 4.9%), and spinal cord (11.3 ﾘ 0.2 nM / 15.2 4.5%). Maximum stimulation for these three membranes were significantly different (P ]GTPS binding dose-response curve, but the other opioid receptor antagonists had no effect. Conclusions: Maximum stimulation of []GTPS binding by OFQ in each membrane showed significantly different profiles, suggesting different pharmacologic efficacies by region. The OFQ-stimulated []GTPS bindings in this study were mediated via nociceptin-opioid peptide receptor stimulation.