Astroglial S100B Secretion Is Mediated by Ca²⁺ Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and...

S100B, a homodimeric Ca²⁺-binding protein, is produced and secreted by astrocytes, and its extracellular levels have been used as a glial marker in brain damage and neurodegenerative and psychiatric diseases; however, its mechanism of secretion is elusive. We used primary astrocyte cultures and calcium measurements from real-time fluorescence microscopy to investigate the role of intracellular calcium in S100B secretion. In addition, the dimethyl sulfoxide (DMSO) effect on S100B was investigated in vitro and in vivo using Wistar rats. We found that DMSO, a widely used vehicle in biological assays, is a powerful S100B secretagogue, which caused a biphasic response of Ca²⁺ mobilization. Our data show that astroglial S100B secretion is triggered by the increase in intracellular Ca²⁺ and indicate that this increase is due to Ca²⁺ mobilization from the endoplasmic reticulum. Also, blocking plasma membrane Ca²⁺ channels involved in the Ca²⁺ replenishment of internal stores decreased S100B secretion. The DMSO-induced S100B secretion was confirmed in vivo and in ex vivo hippocampal slices. Our data support a nonclassic vesicular export of S100B modulated by Ca²⁺, and the results might contribute to understanding the mechanism underlying the astroglial release of S100B.