BACKGROUND: Dynorphin A (1-17) is conceived as an endogenous opioid peptide with a high degree of selectivity forkappa- opioid receptor even though it has been reported to sometimes act like aµ- opioid agonist. The aim of this study was to investigate [³⁵S] GTPγS binding stimulated activation by dynorphin A (1-17) in the cerebral and thalamic membranes of a rhesus monkey.

METHODS: The rhesus monkey ( Macaca mulatta , male, n = 1) was euthanized for the preparation of the cerebral and thalamic membranes. Protein concentrations were determined by the Bradford method. In the dynorphin A (1-17)-stimulated [³⁵S] GTPγS binding dose-response curve, EC₅₀ (effective concentration 50 nM) and maximum stimulation (% over basal) were determined in the absence or presence of theµ-andκ-opioid receptor antagonists naloxone (20 nM) and norbinaltorphimine (nor-BNI, 3 nM), respectively. E2078-stimulated [³⁵S] GTPγS binding was also determined in the absence or presence ofµ-andκ-opioid receptor antagonists in the cortical membrane and compared with dynorphin A (1-17).

RESULTS: Values of EC₅₀ and maximum stimulation of dynorphin A (1-17)-stimulated [³⁵S] GTPγS binding were as follows: cortex (474 nM/32.0%) and thalamus (423 nM/45.3%). Nor-BNI (3 nM) did not antagonize dynorphin A (1-17)-stimulated [³⁵S] GTPγS binding at all in cortical or thalamic membrane, but naloxone (20 nM) produced a 12.2 fold rightward shift of the dynorphin A (1-17)-stimulated [³⁵S] GTPγS binding dose-response curve in the thalamic membrane. The EC₅₀ and the maximum stimulation of E2078-stimulated [³⁵S] GTPγS binding were 65.6 nM and 22.7%, respectively. In E2078-stimulated [³⁵S] GTPγS binding, the dose-response curve was antagonized not by nor-BNI but by naloxone but in the cortical membrane (a 14.2 times rightward shift).

CONCLUSIONS: Dynorphin A (1-17) is selective forµ-opioid receptor in agonist-stimulated [³⁵S] GTPγS binding in the cortical and thalamic membranes of rhesus monkey.