ヒスタミン遊離をめぐる最近の展開

シグナル伝達と細胞機能調節

抄録

An increase in inositol 1, 4, 5-trisphosphate (IP₃) formation in rat mast cells precedes an elevation in intracellular Ca²⁺ levels, which triggers the process(es) leading to histamine release. By means of a transmission electron microscope, it was revealed that when permeabilized mast cells were exposed to potassium antimonate, antimonate precipitates in the endoplasmic reticulum (ER) in the form of calcium antimonate, indicating that the ER is the intracellular Ca store in rat mast cells. IP3 at concentrations higher than 0.5 μM preferentially releases Ca²⁺ from the isolated ER of mast cells. GTP was also effective in releasing Ca²⁺ from the ER. IP₃-induced Ca²⁺ release was inhibited by pretreatments with cAMP and antiallergic drugs. An increase in the intracellular Ca²⁺ concentration may lead to an activation of calmodulin, C kinase and cytoskeletal elements in sequence. Furthermore, microtubules may play an important role in the process (es) leading to Ca²⁺ release from the intracellular Ca store and subsequent histamine release, without affecting IP₃ formation. In contrast, microfilaments seem to participate not only in the extrusion but also in the reincorporation of the mast cell granules, having no influence on intracellular Ca²⁺ release. Substance P (SP) is one of the most effective neuropeptides for releasing histamine from mast cells. Structure-activity relationship studies indicate that basicity at the N-terminal and hydrophobicity at the C-terminal are requisite for its histamine releasing activity. SP effectively released Ca²⁺ from the intracellular Ca store. The site of action of SP on the mast cell surface seems to be the same as that of compound 48 /80. Eosinophil major basic protein (MBP) and histone are also effective for releasing histamine. The cDNA sequences of two subclasses of guinea pig MBP have been determined. These proteins may be released at the site of inflammation from the cells activated by the chemical mediators released from mast cells, and consequently, mast cell activation was reinforced. Such cell-to-cell interaction may be the reason for the augmentation of inflammation.