Kappa-opioid receptor stimulation abolishes mu- but not delta-mediated inhibitory control of spinal Met-enkephalin release.
The possible opioid control through delta, mu and kappa receptors of the spinal release of Met-enkephalin-like material (MELM) was investigated in halothane-anaesthetized rats. The intrathecal perfusion of the delta agonist DTLET (10 microM) or the mu agonist DAGO (10 microM) resulted in a marked inhibition of MELM release, which could be prevented by the selective antagonists naltrindole and naloxone, respectively. Although the kappa agonist U 50488 H (10 microM) was inactive per se, it completely suppressed the inhibitory effect of DAGO, without affecting that of DTLET. As the selective kappa antagonist norbinaltorphimine blocked the action of U 50488 H, it can be concluded that kappa receptors modulate the mu- (but not the delta-) mediated feed back control of spinal enkephalinergic neurones.
Collin
E
E
INSERM U 288, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Bourgoin
S
S
Ferhat
L
L
Hamon
M
M
Cesselin
F
F
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009019:Morphinans / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D004745:Enkephalins; D007211:Indoles; D009019:Morphinans; D009842:Oligopeptides; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D004744:Enkephalin, Methionine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C037653:deltakephalin; C055382:naltrindole