Lack of histamine synthesis and down-regulation of H-1 and H-2 receptor mRNA levels by dexamethasone in cerebral endothelial cells

The purpose of this work was to determine whether cerebral endothelial cell s have the capacity to synthesize histamine or to express mRNA of receptors that specifically respond to available free histamine. The histamine conce ntrations and the expression of L-histidine decarboxylase (HDC) and histami ne H-1 and H-2 receptor mRNA, both in adult rat brain and in cultured immor talized RBE4 cerebral endothelial cells, were investigated. In this study e ndothelial cells were devoid of any kind of detectable histamine production , both in vivo and in the immortalized RBE4 cells in culture. Both the immu nostainings for histamine and the in situ hybridizations for HDC were negat ive, as well as histamine determinations by HPLC, indicating that endotheli al cells do not possess the capacity to produce histamine. Also, glucocorti coid (dexamethasone) treatment failed to induce histamine production in the cultured cells. Although the cerebral endothelial cells lack histamine pro duction, a nonsaturable uptake in RBE4 cells is demonstrated. The internali zed histamine is detected both in the cytoplasm and in the nucleus, which c ould indicate a role for histamine as an intracellular messenger. Histamine H-1 and H-2 receptor mRNA was expressed in RBE4 cells, and glucocorticoid treatment down-regulated the mRNA levels of both H-1 and H-2 receptors. Thi s mechanism may be involved in glucocorticoid-mediated effects on cerebrova scular permeability and brain edema.