The neuropeptide FF analogue, 1DME, enhances in vivo met-enkephalin release from the rat spinal cord.
Behavioural studies have suggested that endogenous opioids mediate the antinociceptive action of neuropeptide FF (FLFQPQRF-NH2) at the spinal level in the rat. This hypothesis was directly assessed by investigating the effects of a NPFF analogue, 1DMe ([D-Tyr1,(NMe)Phe3]NPFF), on the spinal outflow of met-enkephalin-like material (MELM) in halothane-anaesthetised rats. Intrathecal infusion (0.1 ml/min) of 1DMe (0.1 microM-0.1 mM, for 45 min) produced a concentration-dependent increase in spinal MELM outflow which persisted for at least 90 min at the highest concentration tested. Intrathecal coadministration of the micro-opioid receptor antagonist CTOP (1 microM) did not significantly affect the spinal MELM overflow due to 0.1 mM 1DMe. In contrast, both naltrindole and nor-binaltorphimine, at concentrations (10 microM) that allow the selective blockade of alpha- and kappa-opioid receptors, respectively, significantly reduced the stimulatory effect of 1DMe on spinal MELM outflow. These data provide the first direct demonstration that met-enkephalin (among other opioid peptides) can mediate the antinociceptive action of NPFF at the spinal level in rats. In addition, they suggest that reciprocal excitatory interactions between opioids and opioid-modulatory factors (such as NPFF) participate in the physiological control of nociception.
Ballet
S
S
NeuroPsychoPharmacologie Moléculaire Cellulaire et Fonctionnelle, INSERM U288, Faculté de Médecine Pitté-Salpêtrière, Paris, France. ballet@ext.jussieu.fr
Mauborgne
A
A
Gouardères
C
C
Bourgoin
A S
AS
Zajac
J M
JM
Hamon
M
M
Cesselin
F
F
D000700:Analgesics / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D004744:Enkephalin, Methionine / Q000378:metabolism*; D006221:Halothane; D008297:Male; D009292:Narcotic Antagonists; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D000700:Analgesics; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011957:Receptors, Opioid; C105455:neuropeptide FF, Tyr(1)-N-methyl-Phe(3)-; D004744:Enkephalin, Methionine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D006221:Halothane