The effects of RB101, a mixed inhibitor of enkephalin-catabolizing enzymes, on carrageenin-induced spinal c-Fos expression are completely blocked by β-funaltrexamine, a selective μ-opioid receptor antagonist

• Published in: Brain research Vol. 834; no. 1; pp. 200 - 206
• Main Authors: Le Guen, Stéphanie, Honoré, Prisca, Catheline, Gwénaëlle, Fournié-Zaluski, Marie-Claude, Roques, Bernard-Pierre, Besson, Jean-Marie
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 10.07.1999; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; c-Fos; Carrageenan - pharmacology; Carrageenin; Central nervous system; Disulfides - antagonists & inhibitors; Disulfides - pharmacology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Male; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Neprilysin - antagonists & inhibitors; Phenylalanine - analogs & derivatives; Phenylalanine - antagonists & inhibitors; Phenylalanine - pharmacology; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; RB101; Receptors, Opioid, mu - antagonists & inhibitors; Spinal cord; Spinal Cord - metabolism; Vertebrates: nervous system and sense organs; β-Funaltrexamine; μ-Opioid receptor; RB101; μ-Opioid receptor; β-Funaltrexamine; c-Fos; Spinal cord; Carrageenin; Nociception; Rat; Rodentia; Enkephalin; μ Opioid receptor; Enzyme inhibitor; Gene expression; Neuropeptide; Opioid peptide; Vertebrata; Mammalia; Catabolism; Antagonist; Protooncogene; Immediate early gene
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(99)01569-3

We have demonstrated that pre-administered RB101 (40 mg/kg, i.v.), a mixed inhibitor of enkephalin-catabolizing enzymes, decreased spinal c-Fos expression induced 1 h and 30 min after intraplantar (i.pl.) carrageenin (41% reduction, p<0.01). These effects were completely blocked by pre-administered β-funaltrexamine (10 mg/kg, i.v., 24 h prior to stimulation), a selective long-lasting μ-opioid receptor antagonist. In conclusion, these results clearly demonstrate that the effects of endogenous enkephalins on noxiously evoked spinal c-Fos expression are essentially mediated via μ-opioid receptors.