Maton P N, Pradhan T, Moore S
Digestive Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Peptides. 1990 Nov-Dec;11(6):1163-7. doi: 10.1016/0196-9781(90)90147-w.
We have previously described that [Tyr0]CGRP(28-37) acts as a receptor antagonist of rat CGRP in guinea pig pancreatic acini. We therefore examined other C-terminal peptides of CGRP for such activity. CGRP-acetyl(28-37) acetate did act as a rat CGRP antagonist. However, C-terminal CGRP peptides of 4 to 8 amino acid residues did not antagonize the actions of rat CGRP but stimulated amylase secretion. In pancreatic acini, a maximally effective concentration of rat CGRP (100 nM) caused a 2.1-fold increase in amylase secretion. When the C-terminal peptides of CGRP were tested in at 100 microM, CGRP(34-37) caused a 1.8-fold increase in amylase secretion, CGRP(33-37) a 2.8-fold increase. CGRP(32-37) a 9.2-fold increase, CGRP(31-37) a 4.1-fold increase, and CGRP(30-37) a 5.1-fold increase. Further studies with the most effective peptide, CGRP(32-37), demonstrated that it did not cause release of lactate dehydrogenase, and thus did not cause amylase release by cell damage. Unlike rat CGRP, CGRP(32-37) did not increase cellular cyclic AMP, but did stimulate outflux of 45Ca. CGRP(32-37)-stimulated amylase release was not inhibited by the substance P receptor antagonist, spantide, by the bombesin receptor antagonist, [D-Phe6]bombesin(6-13) propylamide, or by the muscarinic receptor antagonist, atropine, but was inhibited by the CCK receptor antagonist L364,718. C-terminal peptides of CGRP inhibited binding of 125I-BH-CCK-8, with the relative potencies of the peptides being the same as their relative potencies for stimulating amylase secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前曾描述过，[Tyr0]CGRP(28 - 37)在豚鼠胰腺腺泡中作为大鼠CGRP的受体拮抗剂发挥作用。因此，我们研究了CGRP的其他C末端肽段的这种活性。CGRP - 乙酰(28 - 37)乙酸盐确实起到了大鼠CGRP拮抗剂的作用。然而，4至8个氨基酸残基的C末端CGRP肽段并不拮抗大鼠CGRP的作用，反而刺激淀粉酶分泌。在胰腺腺泡中，大鼠CGRP的最大有效浓度（100 nM）使淀粉酶分泌增加了2.1倍。当以100 microM测试CGRP的C末端肽段时，CGRP(34 - 37)使淀粉酶分泌增加了1.8倍，CGRP(33 - 37)增加了2.8倍，CGRP(32 - 37)增加了9.2倍，CGRP(31 - 37)增加了4.1倍，CGRP(30 - 37)增加了5.1倍。对最有效的肽段CGRP(32 - 37)的进一步研究表明，它不会导致乳酸脱氢酶释放，因此不会因细胞损伤而导致淀粉酶释放。与大鼠CGRP不同，CGRP(32 - 37)不会增加细胞内环磷酸腺苷（cAMP），但会刺激45Ca外流。CGRP(32 - 37)刺激的淀粉酶释放不受P物质受体拮抗剂spantide、蛙皮素受体拮抗剂[D - Phe6]蛙皮素(6 - 13)丙酰胺或毒蕈碱受体拮抗剂阿托品的抑制，但受胆囊收缩素（CCK）受体拮抗剂L364,718的抑制。CGRP的C末端肽段抑制125I - BH - CCK - 8的结合，肽段的相对效力与其刺激淀粉酶分泌的相对效力相同。（摘要截短至250字）
