Buprenorphine hydrochloride induces apoptosis in NG108-15 nerve cells

• Published in: European journal of pharmacology 1998-04, Vol.347 (1), p.105-112
• Main Authors: Kugawa, Fumihiko, Arae, Ken, Ueno, Akemichi, Aoki, Masatada
• Format: Article
• Language: English
• Subjects: Analgesics; Analgesics, Opioid - toxicity; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Buprenorphine - toxicity; Buprenorphine hydrochloride; DNA - drug effects; DNA - metabolism; DNA Damage; Kinetics; Medical sciences; Nerve Tissue - cytology; Nerve Tissue - drug effects; Nerve Tissue - metabolism; Neuropharmacology; NG108-15; Pharmacology. Drug treatments; Serine protease; Signal Transduction - drug effects; Tosylphenylalanyl Chloromethyl Ketone - pharmacology; TPCK ( N-tosyl- l-phenylalanyl chloromethyl ketone); Tumor Cells, Cultured
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00080-6

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. Zn 2+, 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.