Activation profiles of opioid ligands in HEK cells expressing delta opioid receptors.
BACKGROUND
The aim of the present study was to characterize the activation profiles of 15 opioid ligands in transfected human embryonic kidney cells expressing only delta opioid receptors. Activation profiles of most of these ligands at delta opioid receptors had not been previously characterized in vitro. Receptor activation was assessed by measuring the inhibition of forskolin-stimulated cAMP production.


RESULTS
Naltrexone and nalorphine were classified as antagonists at delta opioid receptor. The other ligands studied were agonists at delta opioid receptors and demonstrated IC50 values of 0.1 nM to 2 microM, maximal inhibition of 39-77% and receptor binding affinities of 0.5 to 243 nM. The rank order of efficacy of the ligands tested was metazocine = xorphanol > or = fentanyl = SKF 10047 = etorphine = hydromorphone = butorphanol = lofentanil > WIN 44,441 = Nalbuphine = cyclazocine > or = met-enkephalin >> morphine = dezocine. For the first time these data describe and compare the function and relative efficacy of several ligands at delta opioid receptors.


CONCLUSIONS
The data produced from this study can lead to elucidation of the complete activation profiles of several opioid ligands, leading to clarification of the mechanisms involved in physiological effects of these ligands at delta opioid receptors. Furthermore, these data can be used as a basis for novel use of existing opioid ligands based on their pharmacology at delta opioid receptors.
Gharagozlou
Parham
P
Molecular Research Institute, Mountain View, CA 94043, USA. parhamgr@purisima.molres.org
Demirci
Hasan
H
Clark
J David
JD
Lameh
Jelveh
J
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000493:pharmacokinetics; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D008024:Ligands; D009292:Narcotic Antagonists; D009294:Narcotics; D017465:Receptors, Opioid, delta; D005576:Colforsin; D020881:Enkephalin, D-Penicillamine (2,5)-; D000242:Cyclic AMP