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Agonist and antagonist effects of dynorphin A-(1-13) in a thermal antinociception assay in rhesus monkeys

ER Butelman, CP France and JH Woods

Department of Pharmacology, University of Michigan, Ann Arbor, USA.

The agonist and antagonist effects of intravenously administered dynorphin A-(1-13) were characterized in the warm water (50 and 55 degrees C) tail withdrawal assay of antinociception in rhesus monkeys. The peptide dose-dependently elevated tail withdrawal latencies in 50 degrees C water, but was ineffective in 55 degrees C water. The antinociceptive effect of dynorphin was surmountably antagonized by quadazocine (0.1 mg/kg) and nor-binaltorphimine (3.2 mg/kg), but was not antagonized by clocinnamox (0.1 mg/kg); this pattern of antagonism is consistent with a kappa-opioid receptor mediated effect. Pretreatment with dynorphin A-(1-13) (0.032-3.2 mg/kg) antagonized the antinociceptive effects of U50,488 and U69,593 in 55 degrees C water, suggesting a low efficacy action of the peptide at the receptors activated by these kappa agonists. However, dynorphin A-(1-13) (3.2 mg/kg) did not antagonize other kappa agonists: bremazocine (0.018- 0.056 mg/kg) and enadoline (0.0056-0.018 mg/kg). Taken together, these dynorphin A-(1-13) findings support the notion of functional kappa- opioid receptor subtypes, and it appears that dynorphin A-(1-13) has limited efficacy at one of these sites. Finally, dynorphin A-(1-13) (0.32 mg/kg) also antagonized the antinociceptive effects of the mu- agonist etonitazene (0.0018-0.01 mg/kg).

Volume 275, Issue 1, pp. 374-380, 10/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




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