Gastrin is gastrointestinal hormones which is structurally similar in carboxy-terminal amino acids[1]. Gastrin are normally produced at high levels by endocrine (G) cells located in the gastric antrum and proximal duodenal mucosa. Gastrin can activate through the CCK2R several signaling pathways that have been linked to proliferation, cell adhesion, and antiapoptotic effects[2]. Human [Leu15]-gastrin-17 is a synthetic analogue of human gastrin-17 and is considered more stable than natural human [Met15]-gastrin-17 while having the same bioactivity[3]
[Leu15]-Gastrin Ⅰ can be synthesized use the Clt-resin[4]. Gastrin analogues can be hydrolyzed by angiotensin-converting enzyme(ACE), indicated that it is possible that administration of ACE inhibitors, used clinically as antihypertensive drugs, could affect the metabolism of gastrin fragments in vivo[5]
Human [Leu15]-gastrin Ⅰ directly modulated secretin binding to its receptors, that may involve in the inhibitory action of secretin on acid secretion induced by gastrin[1]. Continuous infusion of human [Leu15]-gastrin-17 via osmotic minipumps increased the plasma levels of gastrin. In the rats given the high dose(2.4nmol/kg∙h) of human [Leu15]-gastrin-17, the ECL-cell density, the mucosal histamine concentration and HDC activity increased significantly[3]. Continuous infusion of human [Leu15]-gastrin-17(5nmol/kg∙h) for 6 days induces hypergastrinaemia, and caused both vacuoles and lipofuscin bodies to appear in large numbers, suggesting that gastrin stimulates the development not only of vacuoles but also of lipofuscin, perhaps through enhanced autophagocytosis and/or oxidative stress[6]
References:
[1]. Iwakawa S, Nomura H, et al. Direct modulation of secretin binding sites by gastrin in the rat stomach. J Pharmacobiodyn. 1992;15(8):437-441.
[2]. Ferrand A, Wang TC. Gastrin and cancer: a review. Cancer Lett. 2006;238(1):15-29.
[3]. Ryberg B, Axelson J, et al. Trophic effects of continuous infusion of [Leu15]-gastrin-17 in the rat. Gastroenterology. 1990;98(1):33-38.
[4]. Barlos K, Gatos D, et al. Application of 2-chlorotrityl resin in solid phase synthesis of (Leu15)-gastrin I and unsulfated cholecystokinin octapeptide. Selective O-deprotection of tyrosine. Int J Pept Protein Res. 1991;38(6):555-561.
[5]. Dubreuil P, Fulcrand P, et al. Novel activity of angiotensin-converting enzyme. Hydrolysis of cholecystokinin and gastrin analogues with release of the amidated C-terminal dipeptide. Biochem J. 1989;262(1):125-130.
[6]. Zhao CM, Chen D, et al. ECL cells of the rat stomach: development of lipofuscin in response to sustained gastrin stimulation. Cell Tissue Res. 1998;291(2):315-323.
胃泌素是一种胃肠道激素，其结构类似于羧基末端氨基酸[1]。胃泌素通常由位于胃窦和近端十二指肠粘膜的内分泌 (G) 细胞产生，含量较高。胃泌素可通过 CCK2R 激活数种与增殖、细胞粘附和抗细胞凋亡作用相关的信号通路[2]。人 [Leu15]-gastrin-17 是人 gastrin-17 的合成类似物，被认为比天然人 [Met15]-gastrin-17 更稳定，同时具有相同的生物活性[3]
[Leu15]-Gastrin Ⅰ可用Clt-resin[4]合成。胃泌素类似物可被血管紧张素转换酶(ACE)水解，表明临床上作为降压药使用的ACE抑制剂可能会影响胃泌素片段在体内的代谢[5]
人[Leu15]-胃泌素Ⅰ直接调节胰泌素与其受体的结合，可能参与了胰泌素对胃泌素诱导的胃酸分泌的抑制作用[1]。通过渗透性微型泵连续输注人 [Leu15]-胃泌素-17 会增加胃泌素的血浆水平。在给予高剂量（2.4nmol/kg?h）人[Leu15]-胃泌素-17的大鼠中，ECL-细胞密度、粘膜组胺浓度和HDC活性显着增加<sup >[3]。连续输注人[Leu15]-胃泌素-17(5nmol/kg?h)6天后出现高胃泌素血症，同时大量出现空泡和脂褐素体，提示胃泌素刺激可能通过增强的自噬作用和/或氧化应激，不仅产生液泡而且产生脂褐素[6]