Lavezzo A, Bali J P, Magous R, Lignon M F, Nisato D, Laur J, Castro B, Martinez J
Regul Pept. 1986 Sep;15(2):111-9. doi: 10.1016/0167-0115(86)90081-9.
Boc-Trp-Met-Asp-NH2 was described as the smallest peptidic fragment which presented gastric antisecretory activity. Some pharmacological aspects of a peptide analogue, Boc-Trp-Leu-Asp-NH2 (Boc-WLD-NH2), were studied on the main biological functions of gastrin. This compound was found to inhibit the binding of gastrin to isolated gastric fundic mucosal cells (IC50 50 microM). On pentagastrin-induced gastric acid secretion in the rat, a dose-dependent inhibition was observed with an ID50 of 55 mumol/kg when pentagastrin (1 microgram/kg per h) was continuously infused and with an ID50 of 7.8 mumol/kg when pentagastrin (1 microgram/kg) was bolus i.v. injected. Similar inhibition was observed on acid secretion induced by pentagastrin in the isolated rat gastric mucosa (IC50 100 microM), whereas the tripeptide had no effect when acid output was triggered by histamine. A dose-dependent inhibition with the tripeptide was shown on pentagastrin induced guinea-pig ileum contractions (IC50 31 microM). The compound had no activity on histamine-stimulated guinea-pig atria (histamine H2-receptor). These results suggest some evidence for a selective antigastrin activity.
Boc-Trp-Met-Asp-NH2被描述为具有胃抗分泌活性的最小肽片段。对肽类似物Boc-Trp-Leu-Asp-NH2（Boc-WLD-NH2）的一些药理学方面进行了关于胃泌素主要生物学功能的研究。发现该化合物可抑制胃泌素与分离的胃底黏膜细胞的结合（IC50为50微摩尔）。在大鼠中，当持续输注五肽胃泌素（1微克/千克·小时）时，观察到对五肽胃泌素诱导的胃酸分泌有剂量依赖性抑制，ID50为55微摩尔/千克；当静脉推注五肽胃泌素（1微克/千克）时，ID50为7.8微摩尔/千克。在分离的大鼠胃黏膜中，对五肽胃泌素诱导的胃酸分泌也观察到类似的抑制（IC50为100微摩尔），而当酸分泌由组胺触发时，该三肽没有作用。在五肽胃泌素诱导的豚鼠回肠收缩中，显示出该三肽有剂量依赖性抑制（IC50为31微摩尔）。该化合物对组胺刺激的豚鼠心房（组胺H2受体）没有活性。这些结果为选择性抗胃泌素活性提供了一些证据。
