Opiates and enkephalins inhibit synthesis of gangliosides and membrane glycoproteins in mouse neuroblastoma cell line N4TG1.

When mouse neuroblastoma clonal cell line N4TG1 cells were cultured in the presence of opiates or enkephalins, in the range 10(-6)-10(-10) M for 24 hr, a dose-dependent inhibition of the incorporation of [3H]glucosamine and [14C]-galactose into sialoglycosphingolipids and glycoproteins was observed. The gangliosides most affected comigrated in thinlayer chromatographic systems with GM2 (GalNAc[AcNeu]-Gal-Glc-ceramide), GM1 (Gal-GalNAc[AcNeu]Gal-Glc-ceramide), and GDla (AcNeu-Gal-GalNAc[AcNeu]Gal-Glc-ceramide). The effects were stereospecific and naloxone-reversible. Polyacrylamide gel electrophoresis revealed that the synthesis of a large number of membrane glycoproteins was also stereospecifically inhibited. Synthesis of other proteins and glycoproteins, proteoglycans, DNA, and membrane phospholipids and the rate of cell division were not altered in any specific or stereospecific manner. Moreover, clonal cell lines (neuroblastomas and oligodendroglioma) and human skin fibroblasts, which do not possess opiate receptors, did not respond to opiates or enkephalins in a stereospecific manner.