title: Effect of chronic treatment of ohmefentanyl stereoisomers on cyclic AMP formation in Sf9 insect cells expressing human mu-opioid receptors.
abstract: The binding affinity of ohmefentanyl stereoisomers for mu-opioid receptors and the effect of chronic ohmefentanyl stereoisomers pretreatments on intracellular cAMP formation were investigated in Sf9 insect cells expressing human mu-opioid receptors (Sf9-mu cells). Competitive assay of [3H]ohmefentanyl binding revealed that these isomers had high affinity for micro-opioid receptors in Sf9-mu cells. Isomer F9204 had the highest affinity for mu-opioid receptors with the Ki value of 1.66 +/- 0.28 nM. After pretreated Sf9-mu cells with increasing concentrations of these isomers for 6 h, addition of naloxone (1 microM) precipitated an overshoot of foskolin-stimulated cAMP accumulation. The ability of these isomers to induce cAMP overshoot differed greatly with the order of F9202>F9205>F9208>F9206>F9204>F9207. Of these isomers, F9202 was 2.7-fold less potent than F9204 in receptor binding affinity, but 71.5-fold more potent in ability to induce cAMP overshoot. These results suggested that there was a significant stereo-structural difference among ohmefentanyl stereoisomers in ability to induce naloxone-precipitated cAMP overshoot in Sf9-mu cells.
authors.affiliation: 2nd Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Liu
authors.forename: You
authors.initials: Y
authors.lastname: He
authors.forename: Wen-Qiao
authors.initials: WQ
authors.lastname: Jin
authors.forename: Xin-Jian
authors.initials: XJ
authors.lastname: Chen
authors.forename: Qing-Xiang
authors.initials: QX
authors.lastname: Shen
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Chi
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009021:Morphine Dependence / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D018411:Spodoptera / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D014162:Transfection
chemical_list: D000700:Analgesics; D004338:Drug Combinations; D017450:Receptors, Opioid, mu; D009270:Naloxone; C037016:F 7302; D000242:Cyclic AMP; D005283:Fentanyl