Inhibition of sialoglycosphingolipid (Ganglioside) biosynthesis in mouse clonal lines N4TG1 and NG108-15 by β-endorphin, enkephalins, and opiates

G. Dawson, R. McLawhon, R. J. Miller

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

β-Endorphin, [DAla2,DLeu5]enkephalin (opioid peptides), morphine, and levorphanol inhibited the incorporation of [3H]glucosamine, [14C]galactose, and other isotopic precursors into gangliosides G(m)2 (GalNAc-[NeuAc]Gal-Glc-ceramide), G(m)1 (Gal-GalNAc[NeuAc]-Gal-Glc-ceramide), and G(D1a) (NeuAc-Gal-GalNAc-[NeuAc]Gal-Glc-ceramide) in an opiate receptor-positive clonal mouse neurblastoma cell line N4TG1 and a mouse neuroblastoma x rat glioma hybrid clonal cell line NG108-15, but not in opiate receptor-negative cell cultures. No inhibition of cell division, DNA synthesis, protein, phospholipid, or proteoglycan synthesis was observed in the concentration range 10 μM to 100 pm, but inhibition of cell glycoprotein synthesis was observed. Quantitative analysis of N4TG1 cells following both long and short term exposure to opiates and opioid peptides revealed a reduction in ganglioside content equivalent to that observed in the isotope labeling studies. Inhibition was reversed by the opiate antagonist naloxone in dose-dependent manner. Maximum inhibition in N4TG1 cells was observed after 18 to 36 h of exposure to opiates or opioid peptides, but incorporation returned to normal after 54 to 60 h of continuous exposure to both drug and isotopic precursor. However, the further addition of morphine at 18-h intervals maintained the suppression of ganglioside synthesis. Exposure of cells to agents which raise cyclic AMP levels, such as prostaglandin E1, phosphodiesterase inhibitors, and dibutyryl- or 8-bromo-cyclic AMP derivatives, stimulated ganglioside and glycoprotein synthesis and could overcome the inhibition caused by opioids. The hypothesis that changes in cell surface complex carbohydrate composition in opiate receptor-positive clonal cell lines are the result of changes in cellular cyclic AMP concentrations is discussed.

Original languageEnglish (US)
Pages (from-to)129-137
Number of pages9
JournalJournal of Biological Chemistry
Volume255
Issue number1
StatePublished - 1980

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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