Karlstedt K, Sallmén T, Eriksson K S, Lintunen M, Couraud P O, Joó F, Panula P
Department of Biology, Abo Akademi University, Turku, Finland.
J Cereb Blood Flow Metab. 1999 Mar;19(3):321-30. doi: 10.1097/00004647-199903000-00010.
The purpose of this work was to determine whether cerebral endothelial cells have the capacity to synthesize histamine or to express mRNA of receptors that specifically respond to available free histamine. The histamine concentrations and the expression of L-histidine decarboxylase (HDC) and histamine H1 and H2 receptor mRNA, both in adult rat brain and in cultured immortalized RBE4 cerebral endothelial cells, were investigated. In this study endothelial cells were devoid of any kind of detectable histamine production, both in vivo and in the immortalized RBE4 cells in culture. Both the immunostainings for histamine and the in situ hybridizations for HDC were negative, as well as histamine determinations by HPLC, indicating that endothelial cells do not possess the capacity to produce histamine. Also, glucocorticoid (dexamethasone) treatment failed to induce histamine production in the cultured cells. Although the cerebral endothelial cells lack histamine production, a nonsaturable uptake in RBE4 cells is demonstrated. The internalized histamine is detected both in the cytoplasm and in the nucleus, which could indicate a role for histamine as an intracellular messenger. Histamine H1 and H2 receptor mRNA was expressed in RBE4 cells, and glucocorticoid treatment down-regulated the mRNA levels of both H1 and H2 receptors. This mechanism may be involved in glucocorticoid-mediated effects on cerebrovascular permeability and brain edema.
本研究的目的是确定脑内皮细胞是否有能力合成组胺或表达对游离组胺有特异性反应的受体的mRNA。研究了成年大鼠脑和培养的永生化RBE4脑内皮细胞中组胺浓度、L-组氨酸脱羧酶（HDC）以及组胺H1和H2受体mRNA的表达情况。在本研究中，无论是在体内还是在培养的永生化RBE4细胞中，内皮细胞均未检测到任何组胺产生。组胺免疫染色和HDC原位杂交均为阴性，HPLC法测定组胺结果也为阴性，表明内皮细胞不具备产生组胺的能力。此外，糖皮质激素（地塞米松）处理也未能诱导培养细胞产生组胺。虽然脑内皮细胞缺乏组胺产生能力，但RBE4细胞中存在非饱和性摄取。内化的组胺在细胞质和细胞核中均有检测到，这可能表明组胺作为细胞内信使发挥作用。组胺H1和H2受体mRNA在RBE4细胞中表达，糖皮质激素处理下调了H1和H2受体的mRNA水平。该机制可能参与了糖皮质激素对脑血管通透性和脑水肿的介导作用。
