S‐100 Protein in Clonal Astroglioma Cells Is Released by Adrenocorticotropic Hormone and Corticotropin‐Like Intermediate‐Lobe Peptide

Results indicate that the C‐terminal half of ACTH is responsible for the S‐100 protein release, which was released in serum‐free medium supplemented with adrenocorticotropic hormone (ACTH) and observed in normal rat glioblasts.

Abstract

Abstract: S‐100 protein in clonal GA‐1 and C6 rat glioma cell lines was released in serum‐free medium supplemented with adrenocorticotropic hormone (ACTH). The induction of S‐100 protein release by ACTH was dose‐dependent, showing a half‐maximal release at about 5 μ M , and the S‐100 protein concentration in the medium increased sharply within 3 min, but slightly during further incubation. The S‐100 protein release was apparently accompanied by a decrease in the membrane‐bound form of S‐100 protein in the cell. The S‐100 protein release was induced not by the ACTH 1–24 fragment, which exhibits the known effects of ACTH, but by the ACTH 18–39 fragment, which is designated as corticotropin‐like intermediate‐lobe peptide (CLIP). These results indicate that the C‐terminal half of ACTH is responsible for the S‐100 protein release. The enhancement of S‐100 protein release by ACTH was also observed in normal rat glioblasts. The release induced by ACTH was apparently specific to S‐100 protein, because little release of the cytoplasmic enzymes, creatine kinase, and enolase was observed under the same conditions. High concentrations (5 m M ) of dibutyryl cyclic AMP or dibutyryl cyclic GMP were also found to induce S‐100 protein release; however, catecholamines (epinephrine, norepi‐nephrine, isoproterenol, and dopamine), acetylcholine, and glutamic acid did not enhance the release. The S‐100 protein release was also stimulated by 5 m M ATP, ADP, and GTP, probably by lowering the concentration of Ca 2+ in the medium, because addition of Ca 2+ inhibited the release by the nucleotides (but not by the cyclic nucleotides or ACTH), and 1 m M EGTA could induce the S‐100 protein release from GA‐1 glioma cells.