Mechanisms of vancomycin-induced histamine release from rat peritoneal mast cells

The mechanisms of vancomycin (VCM)-induced histamine release were studied with rat peritoneal mast cells. VCM (> 1 x 10(-3) M) released histamine from the isolated mast cells in a dose-dependent and noncytotoxic manner. In the absence of extracellular Ca2+, the histamine release was reduced markedly. When the intracellular Ca2+ was depleted, it was further decreased. The Fura-2-loaded single mast cells showed a biphasic increase in the intracellular Ca2+ concentration ([Ca2+]i) by VCM: the first transient and the second sustained components. In the absence of extracellular Ca2+, the transient component was unchanged, while the sustained component was eliminated completely. The IP3 content in the mast cells increased within 10 s after the application of VCM. These results suggest that VCM release histamine from rat peritoneal mast cells via an IP3 production and increase in [Ca2+]i.