Biological activity of progastrin posttranslational processing intermediates.
Biological activity of progastrin posttranslational processing intermediates.
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前胃泌素翻译后加工中间体的生物活性。
DOI：
10.1152/ajpgi.1987.252.3.g315
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Yamada,T
中科院分区：
文献类型：
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作者：
Matsumoto,M;Park,J;Sugano,K;Yamada,T
我们最近确定了羧基末端延伸的前胃泌素翻译后加工中间体G细胞的胃窦，并证明它们是共同分泌的胃泌素。为了确定这些中间体的生理意义，我们研究了两种合成胃泌素前体类似物的生物活性，这两种合成胃泌素前体类似物对应于具有羧基末端延伸的六胃泌素，Tyr-Gly-Trp-Met-Asp-Phe-Gly-Arg-Arg（GL-9）和Tyr-Gly-Trp-Met-Asp-Phe-Gly-Arg-Arg（GL-7）对从犬胃底粘膜分离的胃壁和D细胞。这两种类似物是有效的胃泌素十七肽取代125 I-[Leu 15]胃泌素从结合位点上的两种细胞类型和刺激[14 C]氨基比林摄取壁细胞和生长抑素释放D细胞。然而，这两种类似物在这些活性方面的效力比胃泌素十七肽低10（4）至10（5）倍。我们的研究结果表明，前胃泌素加工中间体在正常情况下没有生理相关的行动，并支持的概念，羧基末端酰胺化的肽，如胃泌素需要的生物活性的酰胺部分。
We recently identified carboxyl-terminally extended progastrin posttranslational processing intermediates in G cells of the gastric antrum and demonstrated that they are cosecreted with gastrin. To determine the physiological significance of these intermediates, we examined the biological activity of two synthetic gastrin precursor analogues that correspond to hexagastrin with carboxyl-terminal extensions, Tyr-Gly-Trp-Met-Asp-Phe-Gly (GL-7) and Tyr-Gly-Trp-Met-Asp-Phe-Gly-Arg-Arg (GL-9) on gastric parietal and D cells isolated from canine fundic mucosa. Both analogues were as efficacious as gastrin heptadecapeptide in displacing 125I-[Leu15]gastrin from binding sites on the two cell types and in stimulating [14C]aminopyrine uptake by parietal cells and somatostatin release from D cells. However, both analogues were 10(4)- to 10(5)-fold less potent than gastrin heptadecapeptide in these activities. Our results indicate that progastrin processing intermediates do not have physiologically relevant actions under normal circumstances and support the notion that carboxyl-terminally amidated peptides such as gastrin require the amide moiety for biological activity.