title: Differential pharmacological actions of methadone and buprenorphine in human embryonic kidney 293 cells coexpressing human μ-opioid and opioid receptor-like 1 receptors.
abstract: Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human μ-opioid receptor (MOR) and nociceptin/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity; however, buprenorphine induced compromised AC inhibition. When naloxone was introduced after 30 min incubation with methadone, the AC activity was enhanced. This was not observed in the case of buprenorphine. Enhancement of the AC activity was more significant when the incubation lasted for 4 h, and prolonged exposure to buprenorphine elevated the AC activity as well. The removal of methadone and buprenorphine by washing also obtained similar AC superactivation as that revealed by naloxone challenge. The study demonstrated that methadone and buprenorphine exert initially different yet eventually convergent adaptive changes of AC activity in cells coexpressing human MOR and ORL1 receptors.
authors.affiliation: Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
authors.forename: Cynthia Wei-Sheng
authors.initials: CW
authors.lastname: Lee
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Yan
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chiang
authors.forename: Tsai-Wei
authors.initials: TW
authors.lastname: Hung
authors.forename: Hung-Li
authors.initials: HL
authors.lastname: Wang
authors.forename: Lih-Chu
authors.initials: LC
authors.lastname: Chiou
authors.forename: Ing-Kang
authors.initials: IK
authors.lastname: Ho
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000187:drug effects; D002047:Buprenorphine / Q000494:pharmacology*; D004347:Drug Interactions; D004789:Enzyme Activation; D057809:HEK293 Cells; D006801:Humans; D008691:Methadone / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D018847:Opioid Peptides / Q000819:agonists; D011957:Receptors, Opioid / Q000096:biosynthesis; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000096:biosynthesis; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases; D002047:Buprenorphine; D008691:Methadone; D009270:Naloxone; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human