Agonist and antagonist effects of dynorphin A-(1-13) in a thermal antinociception assay in rhesus monkeys.
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).
Butelman
E R
ER
Department of Pharmacology, University of Michigan, Ann Arbor, USA.
France
C P
CP
Woods
J H
JH
D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001572:Benzofurans / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004399:Dynorphins / Q000378:metabolism*; D006358:Hot Temperature; D008253:Macaca mulatta; D009294:Narcotics / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism*; D011759:Pyrrolidines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors*
D000700:Analgesics; D000701:Analgesics, Opioid; D000889:Anti-Arrhythmia Agents; D001562:Benzimidazoles; D001572:Benzofurans; D009294:Narcotics; D010446:Peptide Fragments; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C026843:dynorphin (1-13); D004399:Dynorphins; C084835:etonitazene; C067110:enadoline