| Studies of G Protein Activation of Orphanin FQ in the Cerebrum, Thalamus and Spinal Cord of Monkeys. |
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Heeseung Lee, Jong In Han |
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Department of Anesthesiology and Pain Medicine, College of Medicine, Ewha Womans University, Seoul, Korea. leehee@ewha.ac.kr |
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| Abstract |
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. |
| Key Words:
GTP gamma S; monkey; opioid receptor antagonists; orphanin FQ |
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