Feedback inhibition of met-enkephalin release from the rat spinal cord in vivo.
The possible existence of a feedback control by endogenous opioids of the spinal release of met-enkephalin-like material was assessed in vivo, in halothane-anesthetized rats whose intrathecal space was continuously perfused with an artificial cerebrospinal fluid supplemented with various opioid-related drugs. Both the intrathecal perfusion of the mu agonist D-Ala2-D-MePhe4-Gly-ol5-enkephalin (DAGO) (10 microM) and the delta agonist Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) (10 microM) produced a significant inhibition of the spinal outflow of met-enkephalin-like material. The effect of DAGO, but not that of DTLET, could be prevented by naloxone (10 microM), and, conversely, the effect of DLTET, but not that of DAGO, was no longer observed in the presence of naltrindole (10 microM). Therefore naloxone and naltrindole acted as potent and selective mu and delta antagonists, respectively, when perfused at 10 microM in the intrathecal space of halothane-anesthetized rats. As expected from the lack of a tonic opioid control of spinal enkephalinergic neurones, neither naloxone nor naltrindole alone affected the spontaneous outflow of met-enkephalin-like material. However, naltrindole, but not naloxone, markedly increased the spinal overflow of met-enkephalin-like material due to intrathecal administration of either porcine calcitonin (10 microM) or the peptidase inhibitors thiorphan (10 microM) plus bestatin (20 microM). These data suggest that delta, but not mu, receptors are involved in a phasic opioid inhibitory control of the release of met-enkephalin-like material in the rat spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)
Collin
E
E
INSERM U 288, Neurobiologie Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Bourgoin
S
S
Mantelet
S
S
Hamon
M
M
Cesselin
F
F
D000818:Animals; D002116:Calcitonin / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000494:pharmacology; D005246:Feedback / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009019:Morphinans / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives*; D009842:Oligopeptides / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism*; D015244:Thiorphan / Q000494:pharmacology
D004745:Enkephalins; D007211:Indoles; D009019:Morphinans; D009842:Oligopeptides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D004744:Enkephalin, Methionine; D009271:Naltrexone; C037653:deltakephalin; D002116:Calcitonin; D015244:Thiorphan; C055382:naltrindole; D007930:Leucine; C012211:ubenimex