Search PubMed⌕ Search

Biomedical subjects

G J Dockray

Publications and source records attributed to G J Dockray.

At least 253 records · Page 14Linked to original sources
PubMed1975

Relative abundance of big and little gastrins in the tumours and blood of patients with the Zollinger Ellison syndrome.

The relative concentrations of big gastrin (G-34) and little gastrin (G-17) were compared in the sera and tumours (gastrinomas) of Zollinger-Ellison syndrome patients. Big and little gastrins were identified in all 10 serum samples and in all 10 tumour biopsies examined. In serum, G-34 (range of concentrations 58-220 000 fmol/ml) was the major form of gastrin and G-17 (22-78 000 fmol/ml) was a minor component; the mean relative abundance of G-17/[G17 + G34]) in serum was 0-18 and the mean relative abundance of G-34 was 0-82. In tumour, however, the opposite was true: G-17 (49-869 000 pmol/g) was the major component and G-34 (45-464 pmol/g) a minor component, and the relative proportions of G-17 and G-34 were 0-73 and 0-27 respectively. Following an intravenous injection of porcine secretin (2-0 U/kg) there was a rapid increase in concentration of all forms of gastrin in the blood, but the increase in G-17 was proportionately greater than that of G-34 (relative abundance of G-17 in basal serum was 0-21 compared with 0-37, five minutes after secretin). Differences in the half lives of G-17 and G-34 may partly explain their relative abundancies in serum and tumour tissue.

Antigen-Antibody Reactions↗
PubMed1975

Molecular forms of gastrin in antral mucosa and serum of dogs.

Instillation of liver extract into antral pouches produced an increase in the serum concentrations of both little (G-17) and big (G-34) gastrins. The molar fraction of G-17 plus G-34 represented by G-17 was about 0.9 in antral mucosa and about 0.3 in serum 3 hr after initiating release with liver extract. The predominance of G-34 in serum can be accounted for only in part by its slower rate of removal from the blood so other factors probably also contribute. Although G-17 contributed only about 30% of the total molar concentration of gastrins in serum, it accounted for about 70% of the acid stimulatory activity because on a molar basis it is about five times more bioactive than G-34.

Animals↗
PubMed1975

Amino terminal gastrin fragment in serum of Zollinger-Ellison syndrome patients.

In addition to the previously described molecular forms of gastrin, a new component has been found in high concentrations in the serum of 6 patients with Zollinger-Ellison syndrome. Serum was fractionated by gel filtration, and ion exchange chromatography, and the new component was identified in eluates by radioimmunoassay using an antibody with specificity for the N-terminal portion of heptadecapeptide gastrin. The precise chemical nature of the new component is not known, but its chromatographic behavior and its reactivity to various antibodies is indistinguishable from that of the natural or synthetic N-terminal 1 to 13 fragment of G-17. The new component is present in gastrinoma tumor tissue. Its concentration in serum of gastrinoma patients increases markedly when secretin is injected.

Antibodies, Neoplasm↗
PubMed1975

Culture of Zollinger-Ellison tumor cells.

We have successfully grown six Zollinger-Ellison tumors in vitro with use of a monlayer tissue culture technique. The initial gastrin concentration in the medium varied between 0 and 100 ng per ml. Many cytoplasmic secretory granules were seen in the cells of one culture population. Gastrin secretion was stimulated by the addition of fresh medium to the culture flasks. Both the culture cells and the medium were found to contain primarily big gastrin (G-34) but smaller amounts of little gastrin (G-17) were also present. Gastrin concentration in the medium decreased with time in culture until no hormone was detected between 2 and 6 weeks, possibly because of endocrine cell dedifferentiation and an increased proportion of fibroblasts in the population.

Animals↗
PubMed1972

The action of scretin, cholecystokinin-pancreozymin and caerulein on pancreatic secretion in the rat.

1. The actions of secretin, cholecystokinin-pancreozymin (CCK-PZ) and caerulein have been studied on the rate of flow and protein secretion from the pancreas of urethane-anaesthetized rats.2. Secretin stimulated the rate of flow of pancreatic juice and also stimulated the secretion of small but significant quantities of protein. Cholecystokinin-pancreozymin and caerulein strongly stimulated both the rate of flow and rate of protein secretion.3. Maximal peak rates of flow of juice stimulated by CCK-PZ (20.3 mul./5 min), were significantly higher than stimulated by secretin (14.0 mul./5 min), but maximal volumes of pancreatic juice secreted in total response to rapid I.V. injections of secretin and CCK-PZ were not significantly different.4. The time course of rates of flow of juice stimulated by CCK-PZ and caerulein were different to those stimulated by secretin. With CCK-PZ and caerulein peak rates occurred earlier and responses declined sooner than with secretin.5. The actions of CCK-PZ, caerulein and secretin on the pancreas of the rat are discussed in the light of the responses evoked in other species. It is concluded that the rat is less sensitive than other spieces to secretin but not CCK-PZ.

Animals↗
PubMedDate not supplied

Isolation from porcine antral mucosa of a hexapeptide corresponding to the C-terminal sequence of gastrin.

The present studies were undertaken to confirm reports of high concentrations of the C-terminal tetrapeptide of gastrin in hog antral mucosa. A method was developed whereby synthetic tetrapeptide added to boiling water extracts of hog antral mucosa could be purified to homogeneity by adsorption to Amberlite XAD2 resin, ion exchange chromatography on DEAE cellulose, and reverse phase HPLC. The product had the amino acid composition of gastrin tetrapeptide. When the same method was used on antral mucosa without prior addition of synthetic G4, several small peaks of material with C-terminal immunoreactivity could be found in DEAE column eluates but none could be unequivocally identified as the tetrapeptide. In the same column runs there was a relatively large peak of immunoreactivity eluting later than the tetrapeptide. This material was purified to homogeneity by HPLC and on the basis of its amino acid composition and sequence was identified as the C-terminal hexapeptide of gastrin.

Animals↗
PubMedDate not supplied

Pro-enkephalin gene derived peptides in the porcine stomach: cellular distribution and molecular forms.

Antisera to the enkephalin variants Met-enk Arg6Phe7 and Met-enk Arg6Gly7Leu8 have been used in immunohistochemistry and radioimmunoassay studies of hog stomach. In the mucosa of the antrum, but not fundus, there was identified a population of immunoreactive endocrine-like cells. When extracts of antral mucosa were fractionated by gel filtration on Sephadex G50 the predominant immunoreactive forms of Met-enk Arg6Phe7 and Met-enk Arg6Gly7Leu8 were found to elute before the standards, and were compatible with N-terminally extended variants. In the muscle layers of both antrum and fundus, immunoreactive nerve fibers were found, these were especially numerous in the myenteric plexus. In extracts of the antral muscle, 50-60% of both Met-enk Arg6Phe7 and Met-enk Arg6Gly7Leu8 immunoreactivity eluted in the position of the standards and the remainder had the properties of N-terminally extended variants. In the fundus muscle the variants accounted for 70-80% of total activity. The results indicate that the proenkephalin gene is expressed in neurones and endocrine cells of the hog stomach. The different patterns of molecular forms found in different regions of the stomach suggest that the precursor is processed by different pathways in different populations of endocrine cells and neurones.

Animals↗
PubMedDate not supplied

Met5-enkephalin-Arg6-Gly7-Leu8 immunoreactivity in the human gut.

The presence of the proenkephalin A-derived peptide Met5-enkephalin-Arg6-Gly7-Leu8 was demonstrated throughout the human gastrointestinal tract. Highest concentrations of Met5-enkephalin-Arg6-Gly7-Leu8, as assessed by radioimmunoassay, were measured in the separated muscularis externa, while lower levels were found in the submucosa and only small amounts in the mucosa. The results are consistent with a neuronal location of this peptide in the human gut. Over 65% of total immunoreactivity coeluted with the authentic peptide in both molecular exclusion chromatography and HPLC, while most of the remainder activity eluted earlier on gel filtration. The latter material probably represents N-terminally extended Met5-enkephalin-Arg6-Gly7-Leu8. Taken together with previous studies, our results appear to indicate that there are important species differences in post-translational processing of proenkephalin A in gut nerves.

Colon↗
PubMedDate not supplied

Antibodies to the C-terminus of the cholecystokinin precursor: radioimmunoassay and immunohistochemical studies in adult and developing rat gut.

Antibodies to the extreme C-terminal pentapeptide of procholecystokinin, YEYPS (in the single letter notation), have been used in radioimmunoassay and immunohistochemistry to characterize the material in rat intestine. There is a single major immunoreactive peptide in intestinal extracts that has the properties of the C-terminal tryptic peptide of the CCK precursor. Similar material has previously been found in rat brain. In immunohistochemistry, a population of cells in rat small intestine is revealed, these also contain C-terminal gastrin/CCK activity, but for the most part do not react with gastrin-specific antibodies. During postnatal development their numbers increase considerably. We conclude that the C-terminal flanking peptide of proCCK is a useful marker for sites of CCK production.

Animals↗
PubMedDate not supplied

Differential accumulation of catecholamines, proenkephalin- and chromogranin A-derived peptides in the medium after chronic nicotine stimulation of cultured bovine adrenal chromaffin cells.

We have used an antiserum to a synthetic peptide fragment of bovine chromogranin A (ChrgA)[Tyr0] bovine ChrgA (306-313): YLSKEWEDA, together with antibodies to proenkephalin-derived peptides, to measure the release of immunoreactive peptides from nicotine-stimulated cultured bovine adrenal chromaffin cells. Over a period of 6 hr the accumulation of YLSKEWEDA immunoreactivity and Met-enkephalin Arg6Gly7Leu8 (MERGL) immunoreactivity in the medium of 10 microM nicotine-stimulated cells was shown to be biphasic; the initial phase occurred in the first 15-30 min and the second phase reached a peak after 4 hr. In contrast, catecholamine release occurred monophasically over the initial 15-30 min. Investigation of the second phase of peptide accumulation revealed that it was due in part to nicotine-evoked exocytosis and in part to extracellular processing of high molecular weight precursor proteins.

Adrenal Medulla↗