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: F Kugawa, K Arae, A Ueno, M Aoki
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 347 Issue 1 Pg. 105-12 (Apr 17 1998) ISSN: 0014-2999 [Print] Netherlands
• PMID: 9650855 (Publication Type: Journal Article)

Chemical References

• Analgesics, Opioid
• Tosylphenylalanyl Chloromethyl Ketone
• Buprenorphine
• DNA

Topics

• Analgesics, Opioid (toxicity)
• Animals
• Apoptosis (drug effects, physiology)
• Buprenorphine (toxicity)
• DNA (drug effects, metabolism)
• DNA Damage
• Kinetics
• Nerve Tissue (cytology, drug effects, metabolism)
• Signal Transduction (drug effects)
• Tosylphenylalanyl Chloromethyl Ketone (pharmacology)
• Tumor Cells, Cultured