(Leu¹⁵)-Gastrin I (human)

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.