Ferrar J A, Cuthbert A W, Cox H M
Department of Pharmacology, University of Cambridge, U.K.
Eur J Pharmacol. 1990 Aug 10;184(2-3):295-303. doi: 10.1016/0014-2999(90)90621-c.
Somatostatin-14 (SS-14) and somatostatin-28 (SS-28) produce concentration dependent reductions in short-circuit current in rat colonic mucosa. EC50 values of 15.0 and 13.3 nM were obtained for SS-14 and SS-28 respectively while the N-terminal fragments of SS-28, namely somatostatin-(1-12) (SS1-12) and somatostatin-(1-14) (SS1-14) were inactive. Cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) and cyclo(Pro-Tyr-D-Trp-Lys-Thr-Phe) were potent antisecretory peptides, like SS-14 and SS-28; while the putative somatostatin antagonist, cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bzl]) exhibited neither agonist nor antagonist effects. Responses to SS-14 could be regulated by agents which affected the secretory state of the epithelium. Antisecretory effects of SS-14 were markedly attenuated by piroxicam and were restored following piroxicam plus either forskolin or vasoactive intestinal polypeptide (VIP). SS-14 also attenuated secretory responses produced by carbachol, substance P (SP), VIP and alpha- and beta-calcitonin gene related peptide (alpha-, beta-CGRP). Therefore, SS-14 exhibits broad spectrum antisecretory effects in rat descending colon mucosa.
生长抑素 - 14（SS - 14）和生长抑素 - 28（SS - 28）可使大鼠结肠黏膜的短路电流呈浓度依赖性降低。SS - 14和SS - 28的半数有效浓度（EC50）值分别为15.0和13.3 nM，而SS - 28的N端片段，即生长抑素 -（1 - 12）（SS1 - 12）和生长抑素 -（1 - 14）（SS1 - 14）则无活性。环（脯氨酸 - 苯丙氨酸 - D - 色氨酸 - 赖氨酸 - 苏氨酸 - 苯丙氨酸）和环（脯氨酸 - 酪氨酸 - D - 色氨酸 - 赖氨酸 - 苏氨酸 - 苯丙氨酸）是强效抗分泌肽，与SS - 14和SS - 28类似；而假定的生长抑素拮抗剂环（7 - 氨基庚酰基 - 苯丙氨酸 - D - 色氨酸 - 赖氨酸 - 苏氨酸[苄基]）既无激动剂作用也无拮抗剂作用。对SS - 14的反应可受影响上皮分泌状态的药物调节。吡罗昔康可显著减弱SS - 14的抗分泌作用，而在吡罗昔康加福司可林或血管活性肠肽（VIP）后可恢复。SS - 14还可减弱卡巴胆碱、P物质（SP）、VIP以及α - 和β - 降钙素基因相关肽（α -、β - CGRP）所产生的分泌反应。因此，SS - 14在大鼠降结肠黏膜中表现出广谱抗分泌作用。
