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 u se of peptide mu- and delta -receptor agonists [D-Ala(2), N-me-phe, Gly(5)- ol]-enkephalin (DAMGO) and [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE) and non- peptide agonists ohmefentanyl (OMF) and BW373U86 on the transcription of op ioid receptors of cultured NG108-15 cell and SHSY5Y cells, respectively usi ng the method of reverse transcription-polymerase chain reaction (RT-PCR). It was found that (1) The abundance of mu- and delta- receptor mRNA decreas ed significantly up to 48h after the administration of DAMGO and DPDPE, res pectively; whereas the inhibitory effect of OMF and BW373U86 lasted only fo r 24h; (2) DAMGO and DPDPE produced a significant decrease of the mRNA codi ng for mu -redeptor and 6-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-peptid e opioid agonist to cultured cell line produced a significant decrease of t he gene expression of opioid receptor at transcription level. (2) The effec t of peptide agonists was stronger and lasted longer than that of correspon ding nonpeptide agonists. (C) 2001 Elsevier Science Inc. All rights reserve d.