Buprenorphine hydrochloride induces apoptosis in NG108-15 nerve cells.
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.
Kugawa
F
F
Department of Biological Pharmaceutical Sciences, College of Pharmacy, Nihon University, Chiba, Japan. jfkugawa@sa2.so-net.or.jp
Arae
K
K
Ueno
A
A
Aoki
M
M
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
D000701:Analgesics, Opioid; D014108:Tosylphenylalanyl Chloromethyl Ketone; D002047:Buprenorphine; D004247:DNA