Activity of opioid ligands in cells expressing cloned mu opioid receptors.
BACKGROUND
The aim of the present study was to describe the activity of a set of opioid drugs, including partial agonists, in a cell system expressing only mu opioid receptors. Receptor activation was assessed by measuring the inhibition of forskolin-stimulated cyclic adenosine mono phosphate (cAMP) production. Efficacies and potencies of these ligands were determined relative to the endogenous ligand beta-endorphin and the common mu agonist, morphine.


RESULTS
Among the ligands studied naltrexone, WIN 44,441 and SKF 10047, were classified as antagonists, while the remaining ligands were agonists. Agonist efficacy was assessed by determining the extent of inhibition of forskolin-stimulated cAMP production. The rank order of efficacy of the agonists was fentanyl = hydromorphone = beta-endorphin > etorphine = lofentanil = butorphanol = morphine = nalbuphine = nalorphine > cyclazocine = dezocine = metazocine >or= xorphanol. The rank order of potency of these ligands was different from that of their efficacies; etorphine > hydromorphone > dezocine > xorphanol = nalorphine = butorphanol = lofentanil > metazocine > nalbuphine > cyclazocine > fentanyl > morphine >>>> beta-endorphin.


CONCLUSIONS
These results elucidate the relative activities of a set of opioid ligands at mu opioid receptor and can serve as the initial step in a systematic study leading to understanding of the mode of action of opioid ligands at this receptor. Furthermore, these results can assist in understanding the physiological effect of many opioid ligands acting through mu opioid receptors.
Gharagozlou
Parham
P
Department of Pharmacology, Molecular Research Institute, Mountain View, CA 94043, U.S.A.
Demirci
Hasan
H
Department of Pharmacology, Molecular Research Institute, Mountain View, CA 94043, U.S.A.
David Clark
J
J
Department of Anaesthesiology, VA Palo Alto Health Care System, Palo Alto, CA, 94034, U.S.A.
Lameh
Jelveh
J
Department of Pharmacology, Molecular Research Institute, Mountain View, CA 94043, U.S.A.
D001392:Azocines / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002077:Butorphanol / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism; D005048:Etorphine / Q000494:pharmacology; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D004091:Hydromorphone / Q000494:pharmacology; D008024:Ligands; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011869:Radioligand Assay; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014316:Tritium; D001615:beta-Endorphin / Q000494:pharmacology
D001392:Azocines; D008024:Ligands; D017450:Receptors, Opioid, mu; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D005576:Colforsin; D005048:Etorphine; D009271:Naltrexone; D001615:beta-Endorphin; C012134:SK&F 10047; D009020:Morphine; C034846:lofentanil; D000242:Cyclic AMP; D010620:Phenazocine; D004091:Hydromorphone; D002077:Butorphanol; D005283:Fentanyl; C035969:quadazocine