Teichberg V I, Blumberg S
Prog Biochem Pharmacol. 1980;16:84-94.
A series of C-terminal partial sequences of Substance P, either free or blocked at the amino terminus, has been synthesized. The peptides were examined for their relative potencies as smooth muscle contracting agents and for their rates of degradation by rat brain synaptosomes. The C-terminal hexapeptide in both the free and blocked forms displays activity comparable to that of the longer C-terminal peptides as well as to that of the native undecapeptide. The blocked peptides, however, are much more stable than the corresponding free peptides. Among the free peptides Substance P is degraded virtually at the same rate as the C-terminal octapeptide but significantly more slowly than the C-terminal hexa- or heptapeptides. These patterns of inactivation together with the response to inhibition by various protease inhibitors indicate that both endopeptidase(s) are involved in the degradation of Substance P. Degradation of the Substance P molecule at Substance P synapses may occur in two steps, first by a specific endopeptidase splitting the molecule into an N-terminal tetrapeptide and a C-terminal heptapeptide, the latter being degraded in a second step by aminopeptidases.
已合成了一系列P物质的C末端部分序列，这些序列在氨基末端要么是游离的，要么是封闭的。检测了这些肽作为平滑肌收缩剂的相对效力以及它们被大鼠脑突触体降解的速率。游离形式和封闭形式的C末端六肽显示出与较长的C末端肽以及天然十一肽相当的活性。然而，封闭的肽比相应的游离肽稳定得多。在游离肽中，P物质的降解速率实际上与C末端八肽相同，但明显比C末端六肽或七肽慢得多。这些失活模式以及对各种蛋白酶抑制剂抑制作用的反应表明，两种内肽酶都参与了P物质的降解。P物质分子在P物质突触处的降解可能分两步进行，首先由一种特异性内肽酶将分子裂解为一个N末端四肽和一个C末端七肽，后者在第二步中被氨肽酶降解。
