A BINDING-SITE ON MAST-CELLS AND BASOPHILS FOR THE ANTI-ALLERGIC DRUG CROMOLYN
A BINDING-SITE ON MAST-CELLS AND BASOPHILS FOR THE ANTI-ALLERGIC DRUG CROMOLYN
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DOI：
10.1038/286722a0
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发表时间：
1980-01-01
期刊：
影响因子：
64.8
通讯作者：
PECHT, I
中科院分区：
文献类型：
--
作者：
MAZUREK, N;BERGER, G;PECHT, I
嗜碱性粒细胞和肥大细胞膜的钙通透性在变应原与其特定的膜结合的IgE1-3结合时被刺激。这种钙离子进入细胞触发脱颗粒和分泌过程。色甘酸二钠(l，3-bis(-2-carboxychromon-5-yloxy)-2-hydroxypropane，)可抑制过敏介质的脱颗粒和释放，已广泛应用于过敏性哮喘5-7的治疗。越来越多的证据表明，这种抑制作用是通过阻断钙摄取8，9而发生的。为了定位其作用部位，药物被共价连接到荧光微球(直径分别为0.7m和0.2um)。我们在这里表明，这些药物珠联合物(DBC)确实阻止药物渗透到细胞中，而不会降低其抑制组胺释放的能力(表1)。此外，我们还发现DBC与大鼠腹膜肥大细胞(RPMC)和嗜碱性粒细胞膜上的钙离子依赖结合。
Calcium permeability of basophil and mast cell membranes is stimulated on allergen binding to its specific membrane-bound IgE1–3. This entry of Ca2+ions into the cell triggers the degranulation and secretion process4. Disodium cromoglycate (cromolyn DSCG), the disodium salt of l,3-bis(-2-carboxychromon-5-yloxy)-2-hydroxypropane, inhibits the degranulation and release of anaphylactic mediators, and has found wide application in the treatment of allergic bronchial asthma5–7. Accumulated evidence indicates that this inhibition takes place by blocking the calcium uptake8,9. To localize its site of action, the drug has been covalently conjugated to fluorescent poly-acrylamide and polyglutaraldehyde beads (0.7 and 0.2 µm in diameter, respectively)10. We show here that these drug–bead conjugates (DBC) do prevent the drug penetrating into the cell without reducing its ability to inhibit histamine release (Table 1). Furthermore, we show a specific Ca2+-dependent binding of the DBC to the membranes of rat peritoneal mast cells (RPMC) and basophils.