Carson M R, Shasby S S, Shasby D M
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Am J Physiol. 1989 Oct;257(4 Pt 1):L259-64. doi: 10.1152/ajplung.1989.257.4.L259.
Histamine increases microvascular permeability through a calcium-dependent process, and histamine occupancy of the H1-receptor increases calcium in cultured endothelial cells. Agents that increase adenosine 3',5'-cyclic monophosphate (cAMP) in endothelial cells prevent the in vivo increase in microvascular permeability that follows histamine exposure. In the current experiments, histamine occupancy of the H1-receptor increased the flux of albumin across monolayers of cultured human umbilical vein endothelial cells (HUVEC). This was prevented by pretreating the cells with theophylline, forskolin, and 8-bromo-cAMP (BrcAMP), which also decreased the flux of albumin across control monolayers. Exposing the cells to histamine increased inositol phosphate accumulation in the cells, and this was prevented by the H1-antagonist pyrilamine but not by theophylline, forskolin, and BrcAMP. Exposing the cells to histamine increased intracellular calcium measured with fura-2. The increase in cell calcium was prevented by pyrilamine but not by pretreatment with theophylline, forskolin, and BrcAMP. When endogenous cell GTP was depleted by permeabilizing the membranes of the endothelial cells with Staphylococcus aureus alpha-toxin, histamine-stimulated inositol phosphate accumulation was enhanced with addition of GTP but not with addition of GDP to the buffer. Addition of GTP alone to the buffer did not increase inositol phosphate accumulation in alpha-toxin-treated cells. Histamine stimulates inositol phosphate accumulation in HUVEC via a G protein. Inhibition of the edemagenic effects of histamine by cAMP does not occur by interrupting this signal transduction pathway between the binding of histamine to its receptor and the increase in intracellular calcium.
组胺通过一个钙依赖过程增加微血管通透性，且组胺占据H1受体可使培养的内皮细胞内钙增加。在内皮细胞中增加3',5'-环磷酸腺苷（cAMP）的药物可预防组胺暴露后体内微血管通透性的增加。在当前实验中，组胺占据H1受体增加了白蛋白跨培养的人脐静脉内皮细胞（HUVEC）单层的通量。用茶碱、福斯可林和8-溴-cAMP（BrcAMP）预处理细胞可预防这种情况，这也降低了白蛋白跨对照单层的通量。将细胞暴露于组胺会增加细胞内肌醇磷酸的积累，这可被H1拮抗剂吡苄明阻止，但不能被茶碱、福斯可林和BrcAMP阻止。将细胞暴露于组胺会增加用fura-2测量的细胞内钙。细胞钙的增加可被吡苄明阻止，但不能被茶碱、福斯可林和BrcAMP预处理阻止。当用金黄色葡萄球菌α-毒素使内皮细胞膜通透以耗尽内源性细胞GTP时，添加GTP可增强组胺刺激的肌醇磷酸积累，但向缓冲液中添加GDP则不能。仅向缓冲液中添加GTP不会增加α-毒素处理细胞中肌醇磷酸的积累。组胺通过G蛋白刺激HUVEC中肌醇磷酸的积累。cAMP对组胺致水肿作用的抑制不是通过中断组胺与其受体结合至细胞内钙增加之间的这一信号转导途径而发生的。
