Le Grevès P, Nyberg F, Hökfelt T, Terenius L
Department of Pharmacology, Uppsala, Sweden.
Regul Pept. 1989 Jun-Jul;25(3):277-86. doi: 10.1016/0167-0115(89)90176-6.
Calcitonin gene-related peptide (CGRP) is cleaved by an endopeptidase, also known to hydrolyze substance P (SP). The enzyme which was isolated from human cerebrospinal fluid, converted rCGRP into two products, clearly separable on HPLC. Amino acid analysis showed cleavage to occur at Leu16-Ser17. The carboxy-terminal fragment, rCGRP-(17-37), was weakly active in inhibiting 125I-rCGRP binding to a rat medulla oblongata membrane preparation, but it showed no binding to spinal cord membranes. The N-terminal fragment, rCGRP-(1-16), had very low or no affinity. Autoradiography with 125I-rCGRP showed distinct labelling of rat dorsal spinal cord, while there was no consistent pattern with 125I-rCGRP-(1-16). In the isolated guinea pig ileum preparation, the two fragments showed no CGRP-like activity. The ability of CGRP to interfere with SP degradation is offered as the explanation why CGRP has been reported to potentiate several biologic actions of SP.
降钙素基因相关肽（CGRP）可被一种内肽酶切割，该内肽酶也能水解P物质（SP）。从人脑脊液中分离出的这种酶可将重组CGRP转化为两种产物，在高效液相色谱上可清晰分离。氨基酸分析表明切割发生在Leu16 - Ser17处。羧基末端片段rCGRP-(17 - 37)在抑制125I - rCGRP与大鼠延髓膜制剂结合方面活性较弱，但它与脊髓膜无结合。氨基末端片段rCGRP-(1 - 16)亲和力极低或无亲和力。用125I - rCGRP进行放射自显影显示大鼠背脊髓有明显标记，而125I - rCGRP-(1 - 16)则无一致的标记模式。在分离的豚鼠回肠制剂中，这两个片段无CGRP样活性。CGRP干扰SP降解的能力被认为是CGRP据报道能增强SP多种生物学作用的原因。
