Discrimination between peptide and non-peptide opioid agonists on the transcription of opioid receptors in two cell lines.
The aim of the present study was to characterize the effects of prolonged use of peptide mu- and delta-receptor agonists [D-Ala2, N-me-phe, Gly5-ol]-enkephalin (DAMGO) and [D-Pen2, D-Pen5]-enkephalin (DPDPE) and non-peptide agonists ohmefentanyl (OMF) and BW373U86 on the transcription of opioid receptors of cultured NG108-15 cell and SHSY5Y cells, respectively using the method of reverse transcription-polymerase chain reaction (RT-PCR). It was found that (1) The abundance of mu- and delta- receptor mRNA decreased significantly up to 48h after the administration of DAMGO and DPDPE, respectively; whereas the inhibitory effect of OMF and BW373U86 lasted only for 24h; (2) DAMGO and DPDPE produced a significant decrease of the mRNA coding for mu-receptor and delta-receptor at concentrations as low as 10(-8) mol/L and 10(-6) mol/L, respectively, whereas OMF and BW373U86 were effective at concentrations one order of magnitude higher, respectively. These results suggested that (1) Long-term administration of either peptide or non-peptide opioid agonist to cultured cell line produced a significant decrease of the gene expression of opioid receptor at transcription level. (2) The effect of peptide agonists was stronger and lasted longer than that of corresponding nonpeptide agonists.
Wang
Y
Y
Neuroscience Research Institute, Peking University, Beijing, People's Republic of China.
Wang
X M
XM
Han
J S
JS
D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D017465:Receptors, Opioid, delta / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D001549:Benzamides; D010879:Piperazines; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C083877:BW 373U86; C037016:F 7302; D020881:Enkephalin, D-Penicillamine (2,5)-; D005283:Fentanyl