Down-regulation of 3H-lofentanil binding to opiate receptors in different cultured neuronal cells.
There was stereospecific binding of 3H-lofentanil (KD value = 1.53 nM) to membranes of neuroblastoma-glioma NG 108-15 cells which are known to bear high affinity binding sites for enkephalin derivatives (delta-opiate receptor subtype). There was no high affinity specific binding of the mu-opiate specific ligand 3H-sufentanil. The specific binding of 3H-lofentanil to delta-opiate receptor subtype was down-regulated (decrease in Bmax value without change in the KD value) after prolonged incubation of the cells in the presence of leu- and met- enkephalin (0.1 microM). There was no down-regulation of the opiate receptors (3H-lofentanil and 3H-D-ala-D-leu-enkephalin specific binding) after incubation of NG 108-15 cells with drugs from the fentanyl series (alfentanil or sufentanil). In cultured neurones from rat forebrain (15 day old embryos), the 3H-lofentanil binding was specific with high affinity (KD: 0.048 nM) and a slow dissociation rate similar to that in adult rat cortex. Drugs of the fentanyl series (4-anilino-piperidines) were potent displacers whereas agonists of the delta- (enkephalin derivatives), sigma- (phencyclidine, haloperidol, 3-hydroxyphenyl-propylpiperidine) or K- (U 50488) opiate sites had a low affinity (Ki greater than 0.5 microM) for 3H-lofentanil specific binding sites. Since there was also specific binding of 3H-sufentanil, the opiate receptors in cultured neurones seem to be mainly of the mu-subtype and this is consistent with the ontogeny of opiate receptors subtypes. These receptors were down-regulated after incubation in the presence of etorphine, sufentanil and alfentanil but not enkephalin derivatives.(ABSTRACT TRUNCATED AT 250 WORDS)
Maloteaux
J M
JM
Laboratoire de Neurochimie, Université Catholique de Louvain, Brussels, Belgium.
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Laduron
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D000701:Analgesics, Opioid / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D005910:Glioma / Q000378:metabolism; D009423:Nervous System Neoplasms / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*
D000701:Analgesics, Opioid; D011957:Receptors, Opioid; C034846:lofentanil; D005283:Fentanyl