Mousli M, Trifilieff A, Pelton J T, Gies J P, Landry Y
INSERM U 425, Université Louis Pasteur, Strasbourg I, Illkirch, France.
Eur J Pharmacol. 1995 Mar 15;289(1):125-33. doi: 10.1016/0922-4106(95)90177-9.
Incubation of neuropeptide Y or its C-terminal fragments with rat peritoneal mast cells resulted in a dose-dependent histamine release. Fragment 18-36 of neuropeptide Y was the most biologically active peptide. EC25 value on rat mast cells was 7.2 +/- 2.2 nM. Neuropeptide Y was also able to induce a flare response after intradermal injection in humans. The histamine releasing effects of neuropeptide Y related peptides were greatly inhibited by pretreatment of rat mast cells with pertussis toxin or benzalkonium chloride. Neuropeptide Y and C-terminal related peptides also stimulated the GTPase activity of purified heterotrimeric G proteins in a dose-dependent manner from 1 to 50 microM. Binding studies with [125I]neuropeptide Y were unable to provide evidence for the presence of specific binding sites on the surface of mast cells. The alpha helical conformation of neuropeptide Y fragments was studied by measuring the circular dichroism spectra. Neuropeptide Y-(18-36) was the smallest fragment having a strong helical conformation. Our results demonstrate that neuropeptide Y activates mast cells through a non-specific process leading to G protein activation.
将神经肽Y或其C末端片段与大鼠腹膜肥大细胞一起孵育会导致组胺呈剂量依赖性释放。神经肽Y的18 - 36片段是生物活性最强的肽。在大鼠肥大细胞上的EC25值为7.2±2.2 nM。神经肽Y在人体皮内注射后也能够引发风团反应。用百日咳毒素或苯扎氯铵预处理大鼠肥大细胞可极大地抑制神经肽Y相关肽的组胺释放效应。神经肽Y和C末端相关肽还以1至50 microM的剂量依赖性方式刺激纯化的异三聚体G蛋白的GTP酶活性。用[125I]神经肽Y进行的结合研究未能提供肥大细胞表面存在特异性结合位点的证据。通过测量圆二色光谱研究了神经肽Y片段的α螺旋构象。神经肽Y - (18 - 36)是具有强螺旋构象的最小片段。我们的结果表明，神经肽Y通过导致G蛋白激活的非特异性过程激活肥大细胞。
