Biomedical subjects
Publications and source records attributed to G J Dockray.
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Extracts of turkey brain and jejunum contain a factor closely resembling the COOH-terminal octapeptide of porcine cholecystokinin (CCK). Turkey antral extracts contain factors distinguishable in immunochemical and gel filtration properties from the mammalian forms of gastrin and CCK.
Radioimmunoassays using specific bombesin antisera revealed high concentrations of immunoreactivity in the turkey proventriculus, and negligible amounts of activity elsewhere in the gut. In immunohistochemical studies the same antisera revealed abundant endocrine-like cells in proventriculus mucosa, and isolated cells in small intestinal mucosa. In contrast to the rat, immunoreactivity was not demonstrated in nerves.
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1. The actions of chicken and porcine secretins and vasoactive intestinal peptides (VIPs) were compared on the rate of flow and rate of protein secretion from the exocrine pancreas in urethane anaesthetized turkeys and rats. 2. Chicken VIP was about twice as potent as porcine VIP and 100-150 times as potent as chicken and porcine secretins in stimulating the flow of pancreatic juice in the turkey. 3. Porcine secretin was a strong stimulant of the flow of pancreatic juice in the rat, but chicken secretin and the two VIPs were only active in doses 20-50 times higher than those of porcine secretin. 4. Neither the two VIPs nor the two secretins significantly stimulated the rate of pancreatic protein secretion in the turkey or rat. 5. In the turkey I.V. infusion of graded doses of chicken VIP produced graded increases in the flow of pancreatic juice; in the presence of an infusion of a low dose of CCK8 the flow of juice secreted in response to the highest dose of chicken VIP was significantly lower compared with the infusion of VIP alone, and responses to the other doses of VIP were lower but not significantly so. The infusion of chicken secretin reduced the flow of juice in response to infusions of chicken VIP, but the differences were not significant. There was no significant difference in either the rate of flow, or rate of protein secretion from the turkey pancreas in response to an infusion of chicken secretin and CCK8, compared with CCK8 alone. 6. The results cast doubt on the importance of secretin for regulation of the avian pancreas, and suggest instead that VIP might have a physiological role in regulating the flow of pancreatic juice in birds.
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In normal, duodenal ulcer, and gastric ulcer subjects the two main forms of gastrin, G17 and G34, were estimated by radioimmunoassay in fasting serum and after feeding. Two antisera were used: one showing high specificity for G17, the other specific for the common COOH-terminus of G17 and G34 and so allowing estimation of G34 by difference. Basal G17 was similar in gastric ulcer, duodenal ulcer, and normal subjects and the increases of G17 after feeding were also similar in these groups. In contrast, basal G34 was similar in normal and duodenal ulcer subjects but raised in gastric ulcer subjects. After a meal the G34 concentration in both gastric and duodenal ulcer patients was significantly higher than normal. It is concluded that the higher post-prandial gastrin responses in peptic ulcer that have been previously described are due largely to increased G34.
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Peptides identical or related to mammalian gut hormones occur widely, not just in gut endocrine cells but also in central or peripheral nerves, amphibian skin glands, and a variety of invertebrate tissues. The dual distribution in brain and gut was probably already established early in the vertebrate line; representatives of the oldest vertebrate group, the cyclostomes, have cholecystokinin-like factors in gut endocrine cells and in brain. The related sequences of certain gut peptides, notably gastrin and cholecystokinin (CCK), and secretin, glucagon, vasoactive intestinal polypeptide (VIP), and gastric inhibitory peptide (GIP), indicate evolution from common ancestral molecules by gene duplication and divergence. Functionally important residues are conserved. Thus the COOH-terminal pentapeptide common to gastrin and CCK also contains their minimal active fragment. There are also evolutionary changes at the level of the target organ receptor mechanisms: these are also evolutionary changes at the level of the target organ receptor mechanisms; these are illustrated by evidence suggesting that secretin regulates the flow of pancreatic juice in mammals whereas the structurally related peptide VIP has a similar role in birds.
Acid extracts of rat gut and brain contain substances that cross-react in a radioimmunoassay for the amphibian skin tetradecapeptide bombesin. Highest concentrations are present in the fundic part of the stomach, but there are significant amounts throughout the small and large intestine. Concentrations in the brain are highest in the hypothalamus. On gel filtration the rat bombesin-like immunoreactivity eluted as two major peaks. Fractionation of the second peak on cation exchange chromatography resolves this material into two further components. Intravenous infusions of partially purified preparations of the two components separated on gel filtration cause increases in serum gastrin in rats that are similar to those produced by immunochemically comparable amounts of synthetic bombesin.
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