Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enzyme has been partially purified from canine and porcine cerebral cortical extracts that differs from trypsin in that it manifests some degree of hormone specificity since it converts porcine cholecystokinin to smaller immunoreactive forms, i.e., the COOH-terminal dodecapeptide and octapeptide fragments, but fails to convert big gastrin (34 amino acids) to heptadecapeptide gastrin. This enzyme is distinguishable from trypsin not only in substrate specificity, but also in several physiochemical properties. It is not inhibited in the presence of concentrations of lima bean trypsin inhibitor sufficient to inhibit 1 mg of trypsin per ml of incubation mixture. It is inactivated when incubated with substrate at 45 degrees C for 1 hr, whereas trypsin remains fully active when incubated under the same conditions at 55 degrees C. The enzyme elutes in the void volume on Sephadex G-50 and G-75 gel filtration. On sucrose gradient centrifugation, the proteolytic activity associated with trypsin is recovered above albumin but that of the solubilized brain enzyme is recovered below gamma globulin. The enzyme is not detectable in splenic extracts, which do contain nonspecific proteases capable of completely degrading cholecystokinin. Further investigation is required to determine whether the enzyme in the gut that converts cholecystokinin to the bioactive and immunoactive COOH-terminal fragments resembles or is different from the brain converting enzyme.
 ...
PMID:Characterization of a nontrypsin cholecystokinin converting enzyme in mammalian brain. 28 18

The influence of oral trypsin inhibitor (TI) or vehicle (V) during 4 weeks on oral glucose tolerance (OGT) and on the enteroinsular axis (EIA) of insulin, CCK, and gastrin was studied in five beagles. TI improved OGT throughout the 180-min test period. Incremental areas of insulin and gastrin did not differ from 0 to 60 min after TI and V treatment, but both increased significantly from 60 to 180 min after TI. From 0 to 60 min CCK decreased significantly in the TI group, whereas the differences (delta) in hormone changes (insulin, CCK, gastrin) observed during oral and intravenous glucose showed a decrease for their incremental areas during this period. During the 60- to 180-min period this hormone spectrum was reversed into a non-significant increase. We suggest that TI pretreatment improves oral glucose tolerance, possibly owing to decreased intestinal glucose absorption (early test period), augmentation of the incretin effect (later test period), or some unidentified factor.
 ...
PMID:Improvement of oral glucose tolerance in the dog by feeding trypsin inhibitor. Role of the enteroinsular axis. 245 55

Cathepsin-D has been previously reported to cleave intact PTH into PTH-(1-34) and -(35-84) in membranous fractions of rat and bovine kidney. Whether PTH degradation occurs by intact kidney cells, however, has not been examined in detail. We have, therefore, examined this possibility using an opossum kidney (OK) cell line which possesses the characteristics of proximal renal tubules and responds to PTH. PTH radioimmunoreactivity recovered in trichloroacetic acid-soluble products and in fractions eluted from reverse phase HPLC was measured using an antibody directed to the midregion and C-terminus of PTH. In this study, intact OK cells, but not extracellular enzymes, cleaved human (h) PTH-(1-84) into three discrete fragments which were released into the medium in a time- and temperature-dependent fashion. Half-maximal velocity of PTH-degrading activity (PTHDA) was observed at 9 nM hPTH-(1-84). A 1000-fold molar excess of PTH antagonists [hPTH-(3-34) and [Tyr34]hPTH-(7-34)amide] markedly inhibited PTHDA, whereas ACTH, glucagon, or big gastrin did not suppress it, suggesting an involvement of the PTH receptor in PTHDA. This PTHDA was strongly inhibited by phenylmethylsulfonylfluoride and chymostatin, but not by trypsin inhibitor, elastatinal, or inhibitors of aspartic, cysteine, or metalloproteinases, suggesting that it is due to a seryl chymotrypsin-like endopeptidase. Analysis of chymotrypsin-digested products of hPTH-(1-84) eluted from HPLC exhibited five fragments detected by UV absorbance (210 nm), three of which were measurable by PTH RIA, and each corresponded to the three PTH fragments produced by OK cells. All three fragments were predominantly suppressed in the presence of chymostatin, suggesting that chymotrypsin-like activity is solely responsible for PTHDA in intact OK cells. To further explore the cleavage sites of PTH by chymotrypsin, amino acid analysis of chymotrypsin-cleaved products was performed. The results strongly support the conclusion that a chymotrypsin-like enzyme in OK cells cleaved the hormone between residues 23-24, and 34-35 to produce, at least, hPTH-(24-84) and -(35-84). Lysosomal blockers (chloroquine, ammonium chloride, or monensin) did not affect this PTHDA. Our present study indicates that chymotrypsin-like endopeptidase, but not other endopeptidase or lysosomal enzymes, is responsible for the limited hydrolysis of PTH by intact OK cells.
 ...
PMID:Parathyroid hormone degradation by chymotrypsin-like endopeptidase in the opossum kidney cell. 305 60

The effect of dietary soya bean trypsin inhibitor (SBTI) on rat pancreas, stomach, duodenum and two gastrointestinal hormones (gastrin and cholecystokinin (CCK] levels was investigated over a 21 day period. Rats were fed either a complete diet containing 17% protein as casein (control animals), or the same diet supplemented with 1.1% SBTI (test animals). After 21 days the weight of the pancreas in the test group was 90% higher than that in the controls. The stomach antrum, and duodenum showed no change. The gastrin content in the antrum in fasted rats increased after SBTI feeding whereas plasma gastrin levels remained the same. Dietary SBTI had no effect on fasting CCK levels either in duodenal mucosa or in plasma. The results obtained on gastrin values indicate that SBTI stimulates gastrin biosynthesis in the rat antrum but does not alter its release into the circulation. Results obtained on CCK values suggested the following hypothesis: the endocrine tissue of the duodenum, where CCK is synthesized and stored, represents a relatively large reservoir of this hormone. In addition the secretory capacity of this tissue is probably much higher then is required during normal physiological conditions. Therefore, this tissue does not undergo any adaptive changes after prolonged overstimulation by SBTI. The plasma CCK peak following SBTI intake is probably much higher than after control diet, but clearance of CCK from plasma is relatively fast. Consequently, the high levels of CCK after SBTI intake produce overstimulation of pancreatic secretion and in the long term alter the pancreatic function and morphology but return to normal levels in fasting state.
 ...
PMID:Gastrin and cholecystokinin levels in rats fed soya bean trypsin inhibitor. 379 73

We report herein a specific, sensitive, and rapid bioassay for measuring plasma cholecystokinin in rats. Plasma was first passed through octadecylsilylsilica cartridges and the extracts were then tested for their content of cholecystokinin, based on their ability to stimulate amylase release from isolated rat pancreatic acini. Plasma levels of cholecystokinin-octapeptide as low as 0.18 pM were detectable. Gastrin, in contrast, reacted only weakly in this system. Cholecystokinin bioactivity was inhibited by the antagonist dibutyryl cyclic guanosine monophosphate and was eliminated by immunoadsorption with an antibody directed against the carboxyl terminus of cholecystokinin. Plasma cholecystokinin levels in fasting rats as cholecystokinin-octapeptide equivalents were 0.31 +/- 0.05 pM (mean +/- SE) and rose to 6.2 +/- 1.8 pM after feeding. Plasma cholecystokinin levels also increased 30-fold after intragastric instillation of soybean trypsin inhibitor and 15-fold after ethanol instillation. After column chromatography of plasma, two different forms of cholecystokinin were identifiable; one eluted with the octapeptide of cholecystokinin whereas the other most abundant form was intermediate in size between cholecystokinin-33 and cholecystokinin-octapeptide.
 ...
PMID:Bioassay of plasma cholecystokinin in rats: effects of food, trypsin inhibitor, and alcohol. 620 4

The pH dependence of circular dichroism spectra has been studied for dodecyl sulfate complexes formed by 25 proteins and for a random copolypeptide of glutamic acid and alanine. The pH range covered is that in which titration of side-chain carboxyl groups is to be expected. Circular dichroism spectra signify an increase in helical content upon acidification, although in many cases the increase is quite small. For all but three of the proteins studied, the spectral changes are in reasonable agreement with those expected because helix propagation by glutamyl and aspartyl residues is enhanced when the state of the side-chain carboxyl changes from COO- to COOH. This simple explanation seriously underestimates conformational changes reported for gastrin, Kunitz trypsin inhibitor and tropomyosin. Changes in charge density appear to play an important role in these proteins.
 ...
PMID:Helix formation upon acidification of protein-dodecyl sulfate complexes. 682 4

The distribution, molecular form and release of cholecystokinin (CCK)-like activity in extracts of rat small intestine was studied with an in vitro gall-bladder bio-assay. In contrast to the reported heterogeneity of CCK-like immunoreactivity in the intestine, only a single molecular form of CCK-like activity was detected using the bio-assay. 2. The CCK-like activity eluted from Sephadex G50 with a Kav of 0.69, after the triacontriapeptide of cholecystokinin (CCK33) and before cholecystokinin octapeptide 2500, may represent the 22 amino acid peptide of CCK (CCK22). The bio-assay peak of CCK-like activity had pancreozymin activity and CCK/gastrin C terminal immunoreactivity. The CCK-like activity weas readily extracted from the small intestine at neutral pH, but subsequent treatment with cold 0.5 M-acetic acid extracted further CCK-like activity of the same molecular form as that recovered under neutral conditions. 3. The bio-assay detected no CCK-like activity, nor was pancreozymin-like activity found in fractions corresponding to CCK33 or CCK8 after Sephadex G50 chromatography of rat intestinal extracts. 4. Oral trypsin inhibitor was a potent stimulus for the release of CCK-like activity from the upper small intestine of the rat. After oral trypsin inhibitor release, CCK-like activity was rapidly resynthesized.
 ...
PMID:The release of rat intestinal cholecystokinin after oral trypsin inhibitor measured by bio-assay. 732 Sep 18

Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia.
 ...
PMID:Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation. 849 19

We examined the role of CCK-A receptors in acid inhibition by intestinal nutrients. Gastric acid and plasma CCK and gastrin levels were measured in rats with gastric and duodenal fistulas during intragastric 8% peptone and duodenal perfusion with saline, complete liquid diet (CLD; 20% carbohydrate, 6% fat, and 5% protein), and the individual components of CLD. Acid output was significantly inhibited (50-60%) by CLD, lipid, and dextrose. Plasma CCK was significantly increased by CLD (from 2.6 +/- 0.3 to 4.8 +/- 0.5 pM) and lipid (4.6 +/- 0.5 pM). CCK levels 50-fold higher (218 +/- 33 pM) were required to achieve similar acid inhibition by exogenous CCK-8 (10 nmol x kg(-1) x h(-1) iv). Intestinal soybean trypsin inhibitor elevated CCK (10.9 +/- 2.5 pM) without inhibiting acid secretion. The CCK-A antagonist MK-329 (1 mg/kg iv) reversed acid inhibition caused by CLD, lipid, and dextrose. Peptone-stimulated gastrin (21.7 +/- 1.9 pM) was significantly inhibited by CLD (14.5 +/- 3.6 pM), lipid (12.3 +/- 2.2 pM), and dextrose (11.9 +/- 1.5 pM). Lipid and carbohydrate inhibit acid secretion by activating CCK-A receptors but not by altering plasma CCK concentrations.
 ...
PMID:Acid inhibition by intestinal nutrients mediated by CCK-A receptors but not plasma CCK. 1155 12

The potential toxicity of dietary soy trypsin inhibitor (TI) was evaluated in neonatal miniature swine. From 1 to 6 weeks of age, two groups of male piglets were artificially reared in an Autosow and automatically fed either TI or control liquid diet. From 6 to 39 weeks of age, these two groups were fed either TI or control chow diet. A third group, sow control (SC), suckled from birth to 6 weeks of age, were also weaned to control chow from 6 to 39 weeks of age. Clinical chemistry and plasma cholecystokinin (CCK) determined at 6, 18, 30 and 39 weeks of age, and serum amylase activity with gross and histopathological analyses of major organs at 6 and 39 weeks of age are reported. TI had no effect on plasma CCK, serum amylase activity, or numerous clinical chemistry values. TI-fed piglets had a larger relative liver weight at 6 weeks of age. Relative pancreas weight decreased with age but was not affected by TI. Gross and histopathological analyses of major organs, except the spleen, were within normal limits. Increased incidence of extramedullary hematopoiesis was noted in the spleen of the TI group at 6 but not at 39 weeks of age. There was no consistent pattern in immunohistochemical foci for secretin, gastrin releasing polypeptide or CCK, and no change in DNA, RNA, mitotic index or nuclear density of pancreatic cells. At 6 weeks of age, TI increased pancreatic protein and amylase activity but not trypsin or chymotrypsin activity. None of the effects suggested that this dose of TI was toxic to either the neonatal or sexually mature miniature male swine.
 ...
PMID:Pathological evaluation, clinical chemistry and plasma cholecystokinin in neonatal and young miniature swine fed soy trypsin inhibitor from 1 to 39 weeks of age. 1189 9


1 2 Next >>