title: Buprenorphine hydrochloride induces apoptosis in NG108-15 nerve cells.
abstract: A morphine alkaloid derivative, buprenorphine hydrochloride, induces apoptosis in NG108-15 cells. Apoptosis was detected mainly by apoptosis-specific DNA fragmentation and morphological changes. This apoptosis was dose-dependent and the time-course experiment indicated that DNA fragmentation occurred within 4 h after administration of buprenorphine hydrochloride. Specific inhibitors of the previously characterized apoptotic signal cascade as well as antagonists for opioid receptors were tested. Zn2+, herbimycin A, caspase inhibitors YVAD (Ac-Tyr-Val-Ala-Asp-CHO) and DEVD (Ac-Asp-Glu-Val-Asp-CHO), naloxone and naltrindole had no effect on apoptosis-specific DNA fragmentation. The serine protease inhibitor TPCK (N-tosyl-L-phenylalanyl chloromethyl ketone) specifically inhibited apoptosis-specific DNA fragmentation induced by buprenorphine hydrochloride; however, cell viability measurements revealed that cell death still occurred in NG108-15 cells. Thus TPCK pretreatment before buprenorphine hydrochloride administration induced apoptosis-independent cell death, presumably necrosis, in NG108-15 cells. This suggests that an unidentified serine protease, presumably functioning in the buprenorphine hydrochloride-specific death-signal cascade, could be pivotal for the rapid apoptosis observed in NG108-15 cells upon treatment with buprenorphine hydrochloride.
authors.affiliation: Department of Biological Pharmaceutical Sciences, College of Pharmacy, Nihon University, Chiba, Japan. jfkugawa@sa2.so-net.or.jp
authors.forename: F
authors.initials: F
authors.lastname: Kugawa
authors.forename: K
authors.initials: K
authors.lastname: Arae
authors.forename: A
authors.initials: A
authors.lastname: Ueno
authors.forename: M
authors.initials: M
authors.lastname: Aoki
mesh_terms: D000701:Analgesics, Opioid / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002047:Buprenorphine / Q000633:toxicity*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D007700:Kinetics; D009417:Nerve Tissue / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000701:Analgesics, Opioid; D014108:Tosylphenylalanyl Chloromethyl Ketone; D002047:Buprenorphine; D004247:DNA