Gastrin isolation

C69a. Gregory, R. A., and Tracy, H. J., The constitution and properties of two gastrins extracted from hog antral mucosa. Part I. The isolation of two gastrins from hog antral mucosa. Part II. The properties of two gastrins isolated from hog antral mucosa. Gut 5, 103-114 (1964). 

Gregory RA, Tracy HJ, Agawal KL, et al. Aminoacid constitution of two gastrins isolated from Zollinger-Ellison tumour tissue. Gut 10 603-608, 1969. 

Sustained acid hyperscretion, due either (usually) to a duodenal or pancreatic gastrinoma, or to multiple endocrine adenomata, responds well to proton pump inhibition, often requiring high doses. Resection should always be considered as a cure for those with solitary adenomata, as should operation to reverse the retained antrum syndrome (partial gastrectomy where the antrum is inadvertently retained and isolated from acid inhibition, and secretes gastrin continuously). 

The regulation of calcitonin synthesis and release from the parafollicular C cells of the thyroid gland is calcium dependent. Rising serum calcium is the principal stimulus responsible for calcitonin synthesis and release. Other hormones, such as glucagon, gastrin, and serotonin, also stimulate calcitonin release. Calcitonin has been isolated in tissues other than the parafollicular C cells (parathyroid, pancreas, thymus, adrenal), but it is not known whether this material is biologically active. 

Bado, A., Moizo, L., Laigneau, J.P., Delwaide, J., Lewin, M.J.M., 1994. H3-receptor regulation of vascular gastrin and somatostatin releases by the isolated rat stomach. Yale J. Biol. Med. 67, 113-121. 

Bunnett, N.W., et al. 1988. Isolation of endopeptidase-24.11 (EC 3.4.24.11, enkephalinase ) from the pig stomach. Hydrolysis of substance P, gastrin-releasing peptide 10, [Leu5] enkephalin, and [Met5] enkephalin. Gastroenterology 95 952. 

GRP 119) 53 was isolated from porcine mucosae and causes gastrin secretion. The C-terminal decapeptide of GRP is, with the exception of His20, identical with that of bombesin 54, and also coincides with the sequence of the decapeptide neuromedin C 119b,c) [Gly18-Met27]-GRP. Neuromedin C, a porcine spinal-cord peptide that can also be regarded as a bombesin-like peptide, exerts stimulating effects on rat uterine smooth muscle and functions as a neuromediator in the neural communication systems of mammals. 

Bombesin 54 120,121), isolated from frog skin, is thought to have antidiuretic and antihypertensive properties. It stimulates the secretion of gastrin, pancreatic and gastric secretion, and causes contraction of the gallbladder. 

Secretin inhibits postprandial gastrin release (thus decreasing gastric acid secretion) and increases pancreatic exocrine secretion (e.g. of bicarbonate). The secretin receptor (like the GLP-1 receptor and vasoactive intestinal peptide (VIP) receptor) acts via Gas and cAMP elevation. A plant agonist for the secretin receptor has been isolated from the Thai anti-ulcer plant Croton sublyratus (plau-loi) (Table 5.8). 

Since the publication in 1986 (13,16) of the gastrin/cholecystokinin-like leucosulfakinins (LSK s), several additional insect sulfakinins have been structurally characterized (Table II). The structures of the Drosophila sulfakinins (DSK s) were deduced from a gene sequence which was isolated from Drosophila genomic DNA and head cDNA libraries (17). Although expression of the DSK s remains to be demonstrated, sulfated synthetic replicas are biologically active on the isolated cockroach hindgut (Holman, unpublished observation) as predicted by a study (18) which demonstrated that the hexamer, Tyr(S03)-Gly-His-Met-Arg-Phe-NH2, was the "core structure required for myotropic activity. 

The experiment described in the following section illustrates some of the broad properties of gastrin. The study shows that the levels of serum gastrin artd stomach acid secretion both increase after a meal in a human subject. In isolation, this information does not provide evidence that the rise in scrum gastrin generates the release of gastric acid. Additional evidence is needed to make a firm connection between hormonal levels and the behavior of the parietal cells. Therefore, the study also includes an experiment of an invasive nature, that is, infusion of gastrin. Infusion means a slow injection, perhaps over the course of an hour... 

CCK is a linear polypeptide that exists in multiple molecular forms. The first form isolated was the 33-amino acid peptide CCK-33. Other major forms are CCK-8, CCK-39, and CCK-58. In all forms, the five C-terminal amino acids are identical to those of gastrin and are necessary, together with a sulfated tyrosyl residue, for physiological activity. All of the forms of CCK are produced by enzymatic cleavage of a single 115-amino acid precursor, preprocholecystokinin. 

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