BACKGROUND: The aim of this in vitro study was to investigate [35S]GTP gamma S 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 [35S]GTP gamma S binding dose-response curve, EC50 (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 micron-, kappa-, delta-, and nociceptin- opioid receptors respectively.

RESULTS: The values of EC50 and maximum stimulation of [35S]GTP gamma S 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 ± 0.2 nM / 15.2 ± 4.5%). Maximum stimulation for these three membranes were significantly different (P < 0.05). J-113397 produced a 11.8 fold rightward shift in the OFQ-stimulated [35S]GTP gamma S binding dos0e-response curve, but the other opioid receptor antagonists had no effect.

CONCLUSIONS: Maximum stimulation of [35S]GTP gamma S binding by OFQ in each membrane showed significantly different profiles, suggesting different pharmacologic efficacies by region. The OFQ-stimulated [35S]GTP gamma S bindings in this study were mediated via nociceptin-opioid peptide receptor stimulation.