The neuropeptide FF analogue, 1DMe, reduces in vivo dynorphin release from the rat spinal cord.
Intrathecal infusion of the neuropeptide FF analogue, [D-Tyr1, (NMe)Phe3]neuropeptide FF (1DMe; 0.1 microm-0.1 mm) in anaesthetized rats produced a concentration-dependent decrease in the spinal outflow of dynorphin A (1-8)-like material, which persisted for at least 90 min after treatment with 10 microm-0.1 mm of the compound. Co-administration of d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; 1 microm) to block spinal micro-opioid receptors did not modify this effect, whereas naltrindole (10 microm) totally prevented it and nor-binaltorphimine (10 microm) reduced the post-effect. These data suggest that 1DMe triggers the release of endogenous opioids that stimulate mainly delta-opioid receptors, and secondarily kappa-opioid receptors, thereby exerting a negative influence on dynorphin A (1-8)-like material outflow. Because dynorphin has pronociceptive properties, such a decrease in spinal dynorphin A (1-8)-like material release might underlie the long-lasting antinociceptive effects of intrathecally administered neuropeptide FF and analogues.
Ballet
Sébastien
S
NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, INSERM U288, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Braz
Joao
J
Mauborgne
Annie
A
Bourgoin
Sylvie
S
Zajac
Jean-Marie
JM
Hamon
Michel
M
Cesselin
François
F
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000134:cerebrospinal fluid* / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D023421:Models, Animal; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009842:Oligopeptides / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid* / Q000378:metabolism; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D009292:Narcotic Antagonists; D009842:Oligopeptides; D010446:Peptide Fragments; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C080757:tyrosyl-leucyl-N-methylphenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; C051844:norbinaltorphimine; D013004:Somatostatin; D009271:Naltrexone; D004399:Dynorphins; C026770:dynorphin (1-8); C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; C055382:naltrindole