Antagonist-induced opiate receptor upregulation in cultures of fetal mouse spinal cord-ganglion explants.
Chronic exposure of fetal mouse spinal cord-ganglion explants to the opioid antagonist naloxone (10 microM, 7 days) produced a pronounced upregulation of mu opioid receptors. The antagonist action was stereospecific, as it was produced by (-)-, but not by (+)-naloxone, and was dose-dependent. Half-maximal naloxone-induced receptor upregulation occurred after two days; receptor density was maximal at 5 days. Exposure of the explant cultures to naloxone (10 microM) in the presence of the protein synthesis inhibitor, cycloheximide (1 microM; a concentration which blocks greater than 90% protein synthesis) resulted in receptor density changes that were similar to those observed in cultures exposed to naloxone alone. This finding suggests that antagonist-induced opiate receptor upregulation does not require the synthesis of new receptor molecules.
D000818:Animals; D002478:Cells, Cultured; D046508:Culture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D004090:Dihydromorphine / Q000378:metabolism; D005333:Fetus; D005727:Ganglia, Spinal / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009270:Naloxone / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*
D011957:Receptors, Opioid; D009270:Naloxone; D003513:Cycloheximide; D004090:Dihydromorphine