Ohashi T, Watanabe A, Nishigaki T, Azuma H
Department of Medicinal Chemistry, Tokyo Medical and Dental University, Japan.
Jpn J Pharmacol. 1994 Sep;66(1):7-16. doi: 10.1254/jjp.66.7.
When rat mast cells sensitized by IgE antibody were exposed to antigen, transmission electron microscopy revealed alteration of the granules, cavity formation by fusion of the perigranular membrane and granule release by the fusion of the cavity membrane with the mast cell membrane. Scanning electron microscopy disclosed the extrusion of smooth and round bodies from pores formed on the cell surface. These changes were accompanied by the release of histamine. The inhibition of this degranulation by a novel anti-allergic agent, 6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide (PTPC), was evaluated quantitatively as an inhibition of the granule alteration and cavity formation. At a concentration of 100 nM, PTPC inhibited the granule alteration and cavity formation as well as histamine release. In the same concentration, PTPC significantly increased the cyclic AMP content in the mast cells. These results suggest that the inhibition of the morphological changes in mast cells by PTPC might be due to the increased cyclic AMP caused by the agent and plays an important role in the suppression of chemical mediators release.
当用IgE抗体致敏的大鼠肥大细胞暴露于抗原时，透射电子显微镜显示颗粒发生改变，颗粒周围膜融合形成腔，腔膜与肥大细胞膜融合导致颗粒释放。扫描电子显微镜显示从细胞表面形成的孔中挤出光滑的圆形物体。这些变化伴随着组胺的释放。一种新型抗过敏剂6-(1-吡咯烷基)-N-(1H-四氮唑-5-基)-2-吡嗪甲酰胺（PTPC）对这种脱颗粒的抑制作用，通过对颗粒改变和腔形成的抑制进行定量评估。在100 nM的浓度下，PTPC抑制了颗粒改变和腔形成以及组胺释放。在相同浓度下，PTPC显著增加了肥大细胞中的环磷酸腺苷含量。这些结果表明，PTPC对肥大细胞形态变化的抑制可能是由于该药物导致的环磷酸腺苷增加，并且在抑制化学介质释放中起重要作用。
