Morphine reduces the release of met-enkephalin-like material from the rat spinal cord in vivo by acting at delta opioid receptors.
The modulation by morphine of the spinal release of met-enkephalin-like material (MELM) was investigated in anaesthetized rats whose intrathecal space was perfused with an artificial CSF (ACSF). Morphine (10 microM in the ACSF), as well as a mu- (DAGO, 10 microM) or delta opioid receptor agonist (DTLET, 10 microM), significantly decreased the outflow of MELM. The effects of morphine and DTLET were prevented by the delta antagonist, naltrindole (10 microM), but not by naloxone (10 microM). Conversely, naloxone, but not naltrindole, prevented the inhibitory effect of DAGO. Although neither the kappa 1 agonist, U 50488H (10 microM), nor the kappa 1 antagonist, norbinaltorphimine (10 microM), exerted on their own any significant effect, norbinaltorphimine enhanced the inhibitory action of morphine. In contrast to the inhibition induced by morphine (with or without naloxone) which was preventable by 10 microM naltrindole, the inhibition of MELM release by morphine plus norbinaltorphimine was only partly reduced by naltrindole. Thus, concomitant stimulation of mu, delta and kappa 1 receptors might account for the apparent delta opioid receptor-dependent inhibition of MELM release by morphine. Indeed, its potential inhibitory effect through the stimulation of mu receptors (normally prevented by the concomitant stimulation of kappa 1 receptors) becomes efficient only when kappa 1 receptors are blocked.
INSERM U 288, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
E
E
Collin
A
A
Mauborgne
S
S
Bourgoin
J J
JJ
Benoliel
M
M
Hamon
F
F
Cesselin
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 / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C051844:norbinaltorphimine; D004744:Enkephalin, Methionine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C037653:deltakephalin; C055382:naltrindole