Deems R O, Cardinaux F, Deacon R W, Young D A
Sandoz Research Institute, East Hanover, NJ 07936.
Biochem Biophys Res Commun. 1991 Nov 27;181(1):116-20. doi: 10.1016/s0006-291x(05)81389-0.
The peptides amylin and calcitonin-gene related peptide (CGRP) have been shown to have similar effects on glycogen metabolism in vivo and in vitro. However, it is not clear whether they act via separate receptors. Peptide fragments based on the amino acid sequence of amylin or CGRP were evaluated for their ability to inhibit the action of the peptides in vitro. Insulin-stimulated glycogen turnover, as measured by 14C-glycogen accumulation, was inhibited about 70% by amylin (10nM) and 85% by CGRP (10nM). In the absence of exogenous peptide, peptide fragments based on the 8-37 and 10-37 amino acid sequences of rat amylin (10 uM) had no affect on 14C-glycogen accumulation. In the presence of amylin (10nM), the 8-37 and 10-37 fragments blocked amylin-induced inhibition of 14C-glycogen accumulation 100% and 11.4%, respectively. The 8-37 and 10-37 amylin fragments blocked CGRP inhibition of 14C-glycogen accumulation by 23.2% or 28.6%, respectively. The CGRP 8-37 fragment was equally effective as the amylin 8-37 reversing the effects of amylin than at reversing the effects of CGRP. These results demonstrate that amylin (8-37) completely antagonizes the effects of amylin with limited ability to block CGRP. Removing the eighth and ninth amino acids reduced the effectiveness of the inhibitor by about 90%.
已证明肽类物质胰淀素和降钙素基因相关肽（CGRP）在体内和体外对糖原代谢具有相似作用。然而，它们是否通过不同受体发挥作用尚不清楚。对基于胰淀素或CGRP氨基酸序列的肽片段进行了体外抑制这些肽作用能力的评估。通过14C-糖原积累测定的胰岛素刺激的糖原周转，被胰淀素（10nM）抑制约70%，被CGRP（10nM）抑制85%。在无外源肽的情况下，基于大鼠胰淀素8-37和10-37氨基酸序列的肽片段（10μM）对14C-糖原积累无影响。在有胰淀素（10nM）存在时，8-37和10-37片段分别100%和11.4%地阻断了胰淀素诱导的14C-糖原积累抑制作用。8-37和10-37胰淀素片段分别阻断CGRP对14C-糖原积累的抑制作用23.2%或28.6%。CGRP 8-37片段在逆转胰淀素作用方面与胰淀素8-37片段同样有效，但在逆转CGRP作用方面效果较差。这些结果表明，胰淀素（8-37）完全拮抗胰淀素的作用，但阻断CGRP的能力有限。去除第八和第九个氨基酸使抑制剂的有效性降低约90%。
