Yamamura H, Nabe T, Kohno S, Ohata K
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Eur J Pharmacol. 1994 Nov 14;265(1-2):9-15. doi: 10.1016/0014-2999(94)90217-8.
Whether endothelin-1 or -3 is capable of inducing histamine release from the peritoneal mast cells of BALB/c mice was investigated in vitro and compared to the release induced by compound 48/80. In contrast to the mouse bone marrow-derived mast cells, which originated from the same strain and have been reported upon previously, the (both crude and purified) peritoneal mast cells potently secreted histamine in response to either endothelin-1 or endothelin-3 in a concentration-dependent fashion. Even at a concentration as low as 10 nM, endothelin-1 induced a histamine release of more than 50% from the peritoneal mast cells. Cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), an endothelin ETA receptor antagonist, markedly suppressed not only the histamine released induced by endothelin-1 but also that due to endothelin-3 at a similarly low concentration range. Treatment with islet-activating protein (IAP) for 3 h, an inactivator of guanosine triphosphate (GTP) (Gi)-protein, markedly reduced the histamine release induced by endothelin-1. Neomycin at 0.1 and 1 mM or ethylenediaminetetraacetic acid (EDTA) at 0.1 mM in the absence of Ca2+, neither of which affected the histamine release induced by endothelin-1, substantially reduced histamine release caused by compound 48/80. On the other hand, treatment with O-O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester (BAPTA-AM), an intracellular calcium chelating agent, completely inhibited the release induced by both endothelin-1 and compound 48/80. These results indicate that endothelin-1 is one of the most potent histamine releasers in mouse peritoneal mast cells discovered so far.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了内皮素 -1 或 -3 是否能够在体外诱导 BALB/c 小鼠腹腔肥大细胞释放组胺，并与化合物 48/80 诱导的释放进行比较。与源自同一品系且先前已有报道的小鼠骨髓源性肥大细胞不同，（粗制和纯化的）腹腔肥大细胞会以浓度依赖的方式对内皮素 -1 或内皮素 -3 有效分泌组胺。即使在低至 10 nM 的浓度下，内皮素 -1 也能诱导腹腔肥大细胞释放超过 50% 的组胺。内皮素 ETA 受体拮抗剂环（D - 天冬氨酸 - 脯氨酸 - D - 缬氨酸 - 亮氨酸 - D - 色氨酸）（BQ - 123）不仅能显著抑制内皮素 -1 诱导的组胺释放，在相似的低浓度范围内也能抑制内皮素 -3 诱导的组胺释放。用胰岛激活蛋白（IAP）处理 3 小时（一种三磷酸鸟苷（GTP）（Gi）蛋白的失活剂），能显著降低内皮素 -1 诱导的组胺释放。在无 Ca2+ 的情况下，0.1 和 1 mM 的新霉素或 0.1 mM 的乙二胺四乙酸（EDTA），二者均不影响内皮素 -1 诱导的组胺释放，但能大幅降低化合物 48/80 引起的组胺释放。另一方面，用细胞内钙螯合剂双（2 - 氨基苯基）乙二醇 - N,N,N',N' -四乙酸四乙酰甲酯（BAPTA - AM）处理，能完全抑制内皮素 -1 和化合物 48/80 诱导的释放。这些结果表明，内皮素 -1 是迄今为止在小鼠腹腔肥大细胞中发现的最有效的组胺释放剂之一。（摘要截短至 250 字）
