金属内蛋白酶抑制剂对牛肾上腺嗜铬细胞分泌及细胞内游离钙的影响。

Effects of metalloendoproteinase inhibitors on secretion and intracellular free calcium in bovine adrenal chromaffin cells.

作者信息

Harris B, Cheek T R, Burgoyne R D

出版信息

Biochim Biophys Acta. 1986 Oct 31;889(1):1-5. doi: 10.1016/0167-4889(86)90002-9.

Abstract

The possible role of metalloendoproteinase in stimulus-secretion coupling in adrenal chromaffin cells was examined using the metalloendoproteinase inhibitors 1,10-phenanthroline and carbobenzoxy-Gly-Phe-NH2. Catecholamine release elicited by nicotine or by depolarisation with 55 mM K+ was almost completely abolished by 0.5 mM 1,10-phenanthroline. Carbobenzoxy-Gly-Phe-NH2 (2.5 mM) inhibited catecholamine release in response to nicotine but enhanced that due to 55 mM K+. The rise in intracellular free calcium, [Ca2+]i, in response to either nicotine or 55 mM was inhibited by about 50% by both inhibitors. One site of action of metalloendoproteinase inhibitors may, therefore, be at the level of the regulation of [Ca2+]i. Catecholamine release and the rise in [Ca2+]i elicited by the calcium ionophore ionomycin were not reduced by the inhibitors. These results show that metalloendoproteinase inhibitors have complex effects on chromaffin cells including effects on the regulation of [Ca2+]i but do not inhibit calcium-activated exocytosis itself.

摘要

使用金属内蛋白酶抑制剂1,10 - 菲咯啉和苄氧羰基 - 甘氨酸 - 苯丙氨酸 - 氨对肾上腺嗜铬细胞中金属内蛋白酶在刺激 - 分泌偶联中的可能作用进行了研究。0.5 mM的1,10 - 菲咯啉几乎完全消除了尼古丁或55 mM K⁺去极化引发的儿茶酚胺释放。苄氧羰基 - 甘氨酸 - 苯丙氨酸 - 氨（2.5 mM）抑制了对尼古丁的儿茶酚胺释放，但增强了因55 mM K⁺引起的释放。两种抑制剂都使对尼古丁或55 mM K⁺响应的细胞内游离钙[Ca²⁺]i的升高受到约50%的抑制。因此，金属内蛋白酶抑制剂的一个作用位点可能在[Ca²⁺]i的调节水平。钙离子载体离子霉素引发的儿茶酚胺释放和[Ca²⁺]i升高未被抑制剂降低。这些结果表明，金属内蛋白酶抑制剂对嗜铬细胞有复杂的影响，包括对[Ca²⁺]i调节的影响，但不抑制钙激活的胞吐作用本身。