Title: Gastrins
Literature References: Gastrointestinal hormones isolated from the mucosal lining of the gastric antrum of various mammalian species. Highly potent gastric secretion stimulants, first discovered by J. S. Edkins: Proc. Roy. Soc. London 76B, 376 (1905). Several gastrins have been identified; they are referred to as "little gastrin", "big gastrin" and "minigastrin". "Little gastrin" or G-17 exists in two forms, 18-34-gastrin I or G-17-I and 18-34-gastrin II or G-17-II, which are heptadecapeptides that are identical in amino acid sequence, with the latter having sulfated tyrosine residues. There are relatively small species differences in amino acid sequences of G-17, although there are differences in the ratio of the non-sulfated to the sulfated forms. This ratio is about 3:4 in hog compared to about 2:1 in man. "Big gastrin" or 1-34-gastrin, also found in two forms, consists of the heptadecapeptides of "little gastrins" extended from their N-termini by additional heptadecapeptides with amino acid compositions different from G-17. For each species, the G-17-I and G-17-II portions of the G-34 gastrin are identical. Pairs of shorter gastrins, or "minigastrins" (22-34-gastrin) are C-terminal tetradecapeptides. Structure of porcine "little gastrins": Gregory et al., Nature 204, 391 (1964); human: Bentley et al., ibid. 209, 583 (1966). Synthesis of porcine "little gastrins": Anderson et al., ibid. 204, 933 (1964); human: Beecham et al., ibid. 209, 585 (1966); human and canine: Agarwal, Kenner, J. Chem. Soc. C 1969, 2213; ovine: Agarwal et al., ibid. 954; feline: eidem, Experientia 25, 346 (1969). General synthetic method: E. Brown et al., Chem. Commun. 1980, 1093. Isoln of "big gastrins" from Zollinger-Ellison tumor tissue: R. A. Gregory, H. J. Tracy, Lancet 2, 797 (1972). Isoln of "minigastrins" from Zollinger-Ellison tumor tissue: eidem, Gut 15, 683 (1974). Amino acid sequences of porcine and human "big gastrins": eidem, in Gastrointestinal Hormones, J. C. Thompson, Ed. (Univ. Texas Press, Austin, 1975) pp 13-14. Revised sequence of porcine: G. J. Dockray et al., Bioorg. Chem. 8, 465 (1979); of human: A. M. Choudhury et al., Z. Physiol. Chem. 361, 1719 (1980). Synthesis of human: G. Wendlberger et al., Monatsh. Chem. 112, 1297 (1981). Structure and synthesis of "minigastrins": R. A. Gregory et al., Z. Physiol. Chem. 360, 73 (1979). Review of chemical studies: Kenner, Sheppard, Proc. Roy. Soc. London 170B, 89 (1968). Review of physiological advances: Gregory, ibid. 81. General reviews: Sanders, Schimmel, Am. J. Med. 49, 380 (1970); McGuigan, Vitam. Horm. 32, 47-88 (1974); V. Mutt, ibid. 39, 231-426 (1982). |