ABSTRACT

Enkephalin was thought to be exclusively a neuron-specific peptide until 1986 when the C6 glioma cell line was found to synthesize preproenkephalin mRNA and enkephalinimmunoreactive material (Yoshikawa and Sabol, 1986). Glia also were soon shown to be sources for enkephalin in primary cultures of rodent brain cells (Vilijn et ai, 1988; Shinoda et ai, 1989), demonstrating that glial synthesis of enkephalin was not a peculiarity of transformed cell lines. Since then C6 glioma cells and a subset of type 1-like astrocytes in primary brain cell cultures have been repeatedly demonstrated to synthesize and release proenkephalin into the media (Hauseref a/., 1990; Batter, Vilijn and Kessler, 1991; Klein and Flicker, 1992; Mar, Suh and Hong, 1992; Shinoda, Marini and Schwartz, 1992). In contrast to neurons, astrocytes and C6 glioma cells have a limited storage capacity for enkephalincontaining peptides, and secretion appears to be tightly coupled to synthesis; thus media levels of enkephalin-containing peptides can be taken as a convenient index of glial preproenkephalin gene expression. These glial cells also make and release carboxypeptidase E and other non-specific processing enzymes into the media where the bulk of the processing of proenkephalin to enkephalin and other enkephalin-immunoreactive peptides occurs (Klein and Fricker, 1992; Ferro et ai, 1993).