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Biomedical subjects

B Shaw

Publications and source records attributed to B Shaw.

At least 73 records · Page 4Linked to original sources
PubMed1981

Stimulated gastric prostaglandin output, and the effect of inhibition of prostaglandin synthetase, in the conscious cat.

1. In the conscious gastric fistula cat there was no correlation between the outputs of gastric acid and PGE secreted in response to incremental doses of pentagastrin and histamine acid phosphate. 2. PGE secreted in response to pentagastrin and histamine was not dose dependent. 3. Flurbiprofen significantly inhibited the gastric output of PGE but did not influence acid or pepsin secretion. Inhibition of PGE secretion was accompanied by evidence of gastric mucosal haemorrhage. 4. It is concluded that gastric juice PGE is unlikely to be involved in the physiological control of acid secretion.

Animals↗
PubMed1981

Equipotency of little and minigastrin in the cat.

Synthetic human non-sulphated gastrin heptadecapeptide (little gastrin) and tetradecapeptide (minigastrin) are equipotent stimulants of gastric acid and pepsin secretions in the conscious cat. This supports the thesis that minigastrin is a major physiologically active, circulating form of the hormone in the cat. It is estimated that little gastrin and minigastrin contribute equally to the gastric acid response to a protein meal in the cat.

Animals↗
PubMed1980

Non-reducible cyclic, and azaphenylalanyl6 analogues of somatostatin.

SSeven new analogues of somatostatin are described, along with the effects of these analogues on pentagastrin-stimulated gastric acid and pepsin secretion in conscious cats. Replacement of the cystine disulphide bridge of somatostatin with an amide bridge, with or without deletion of the N-terminal dipeptide, resulted in analogues with approximately 20% of the potency of somatostatin. Simultaneous ommision of Lys4 in the amide-bridge analogues reduced the activity of the peptides to approximately 5% of somatostatin. Substitution of Phe6 of somatostatin or an amide-bridged analogue with azaphenylalanyl resulted in peptides with no detectable activity. The results illustrate the possible importance of the basic side-chain of Lys4 for the activity of somatostatin. The lack of activity of azaphenylalanyl6 analogues of somatostatin demonstrate the extreme importance of the orientation of the side-chain of Phe6 for the activity of somatostatin, possibly for the binding to somatostatin receptors.

Amino Acid Sequence↗
PubMed1980

Structure-activity studies with somatostatin: the role of tryptophan in position 8.

The gastric acid and pepsin inhibitory activities of 21 analogues of somatostatin, the majority modified at position 8, were determined in conscious cats in order to examine the importance of Trp8 for the activity of somatostatin. Pepsin secretion stimulated by pentagastrin was 5 times more sensitive, compared with the acid secretion, to inhibition by somatostatin. All the analogues showed similar differential sensitivity, indicating a similar specificity of somatostatin receptors involved in the inhibition of these two secretions. Halogenated-Trp8 analogues of somatostatin were only equipotent or slightly more active than somatostatin against gastric secretion in the cat, whilst these analogues are up to 30 times more potent against growth hormone release in the rat, indicating a different specificity of the two groups of receptors. Studies with the position 8 modified analogues suggest that the electron density of the aromatic nucleus of Trp8 may be relatively unimportant in determining the gastric inhibitory activity, whilst it can be concluded that the role of Trp8 in somatostatin depends to a large extent on the indole NH group. The precise role of Trp8 in somatostatin could be an involvement in the binding of somatostatin to its receptors, or involvement in forming the biologically active conformation of somatostatin.

Animals↗
PubMed1980

Effects of thyrotrophin-releasing hormone, and methionine-enkephalin on gastric acid and pepsin secretion in the cat.

1 The effect of intravenous administration of thyrotrophin-releasing hormone (TRH) and methionine-enkephalin on gastric acid and pepsin secretions was investigated in conscious cats prepared with chronic gastric fistulae.2 TRH, 20 mug kg(-1) h(-1), did not influence unstimulated gastric acid secretion, nor gastric acid secretion stimulated by submaximal doses of pentagastrin or histamine. Pepsin secretion stimulated by pentagastrin was not influenced by TRH.3 TRH, 20 mug kg(-1) h(-1), significantly reduced the gastric acid and pepsin responses to intravenous infusion of insulin. TRH also significantly reduced the degree of hypoglycaemia seen in response to insulin. TRH, 20 mug kg(-1) h(-1), but not 5 mug kg(-1) h(-1), infused alone resulted in a significant hyperglycaemia.4 It is concluded that the reduction of insulin-stimulated gastric secretion by TRH is not dependent on the hyperglycaemic action of the peptide. The mechanism of action of TRH on insulin-stimulated secretion is discussed with respect to its site of action.5 Methionine-enkephalin or the potent analogue, D-Ala(2), Met-enkephalinamide were without effect on unstimulated gastric secretion, or secretion stimulated by pentagastrin, histamine, and insulin. The opiate receptor antagonist, naloxone, did not significantly alter the gastric acid or pepsin response to insulin.6 It is concluded that there is no evidence that opiates stimulate oxyntic glands directly, nor that the oxyntic cells may possess high affinity binding sites for opiates, nor that endogenous opiates are involved in the control of gastric secretion.

Animals↗
PubMed1980

Gastric acid and pepsin-stimulating activity of non-sulphated fragments of gastrin in the cat.

The gastric acid and pepsin-stimulating activities of several C terminal fragments of non-sulphated human gastrin were investigated in the conscious cat prepared with cannulated gastric fistulae with a reproducible, continuous infusion method to construct dose-response curves. The gastric acid-stimulating activities were quantified by reference to the ED50 and were compared with the activity of synthetic non-sulphated human gastrin 17 (SHG17NS) and cat gastrin 17 (SCG17NS). SHG17NS had an ED50 of 0.329 nmol kg-1 h-1. SHG16NS, SHG15NS and SHG13NS all showed similar activities to SHG17NS. SCG17NS tested at low doses had similar activity to SHG17NS. SHG10NS, G5 and G4 and peptavlon showed progressively lower acid-stimulating activities: 26, 12, 9 and 9%, respectively, compared with SHG17NS. The gastric acid-stimulating activities of all the peptides were paralleled by similar pepsin-stimulating activities. The ratios of pepsin secretion:acid secretion were similar for all the peptides (1--2 microgram pepsin/microEq H+). The results are discussed in relation to the biological activity of the circulating gastrin components in the cat compared with other species and it is argued that component IV (corresponding to gastrin tetradecapeptide or minigastrin) is a major, physiologically active, circulating form of the hormone in the cat.

Animals↗
PubMed1979

Effects of a combined oestrogen-progestin preparation on gastric acid and pepsin secretion, serum gastrin concentration and biliary secretion of bile acids, phospholipids, and cholesterol in the cat.

1 Daily ethinyloestradiol (50 mug) and norethisterone acetate (1 mg) treatment (Minovlar) was investigated on gastric acid and pepsin secretion, and fasting serum gastrin concentration in six conscious female cats prepared with chronic gastric fistulae. The effect on biliary secretion of bile acids, phospholipids, and cholesterol was investigated in three conscious female cats prepared with chronic gastric and intestinal fistulae, and cholecystectomy.2 Treatment for 49 days did not alter the gastric acid or pepsin response to either intravenous pentagastrin infusions or a food stimulus. The fasting serum gastrin concentration remained unaltered throughout the study.3 Treatment for 18 days did not alter the percentage concentration of cholesterol in the bile, but reduced the percentage concentration of phospholipid. This was mirrored by a rise in the percentage concentration of bile acids in the bile. These trends were quickly reversed on cessation of treatment.4 There was no sign of cholestasis associated with the treatment. Intestinal flow remained constant throughout the study, there was no lithocholic acid or other abnormal bile acids detectable in any samples, and there was no change in serum aspartate aminotransferase concentration.5 The results suggest that in female cats, treatment with a combined oestrogen-progestin preparation does not exert any beneficial effects on the aetiology of peptic ulceration through the reduction of acid or pepsin secretion, or the lowering of serum gastrin concentration. The preparation shows a tendency to produce more lithogenic bile, and this may partly explain the greater incidence of gall stones in women on the contraceptive pill.

Animals↗
PubMed1979

Endogenous prostaglandins and stimulated gastric secretion in the cat: the effect of various secretory inhibitors.

1. The effects of cimetidine, somatostatin and atropine upon the outputs of acid, pepsin, prostaglandins (PG) E and F in gastric juice secreted in response to i.v. infusions of pentagastrin and histamine (H) have been studied in the conscious gastric fistula cat. 2. At constant rate infusions secretion of PGE occurs and follows a similar pattern to that of gastric acid. However the ratio of H:PGE varies considerably and to an extent inexplicable in terms of assay variation. 3. Inhibition of acid output is matched by inhibition of the output of PGE, but changes in concentration of PGE suggest this is a volume related phenomenon. 4. It is concluded that gastric juice PGE is most unlikely to have a regulatory effect upon acid secretion.

Animals↗
PubMed1978

Structure-activity relationships of eighteen somatostatin analogues on gastric secretion.

1. The effect of somatostatin and eighteen somatostatin analogues on pentagastrin-stimulated gastric acid and pepsin secretion was investigated in the conscious vagotomized cat prepared with chronic gastric fistulae. The majority of the analogues are peptides where D-amino acids are incorporated into the molecule instead of the natural L-isomers. 2. The ID50 for cyclic-somatostatin inhibition of near-maximal gastric acid secretion stimulated by pentagastrin 8 microgram kg-1 hr-1 was found to be 1.29 +/- 0.13 n-mole kg-1 hr-1. Pentagastrin-stimulated pepsin secretion had a lower threshold to somatostatin inhibition than did acid secretion. 3. D-Phe6, D-Phe7, D-Thr10, D-Thr12 and D-Phe6-D-Trp8 analogues all show low biological activity against the secretion of gastric acid and pepsin, growth hormone, insulin and glucagon. None of these analogues are antagonists of the cyclic-somatostatin inhibition of gastric secretion, suggesting that they have low affinity for this somatostatin receptor. 4. The analogues under investigation show parallel changes in activity against gastric and growth hormone secretion, suggesting a similarity between the gastric and growth hormone receptors for somatostatin. 5. D-Cys14 analogues are equipotent with or have a greater potency than cyclic-simatostatin in inhibiting the secretion of gastric acid, growth hormone and glucagon but show low insulin inhibiting activity.

Animals↗
PubMed1978

Exogenous prostaglandins and gastric secretion in the cat.

1. In the conscious gastric fistula cate PGE2 was shown to produce dose-related inhibition of gastric acid and pepsin secreted in response to pentagastrin, histamine and insulin. 2. PGF2alpha had little effect on pentagastrin-stimulated gastric acid and pepsin secretion. 3PGF2 delayed the tachyphylaxis of gastric acid stimulated by pentagastrin and histamine, but not that stimulated by insulin. 4. Although not delaying tachyphylaxis of insulin stimulated acid, PGE2 delayed tachyphylaxis of insulin stimulated pepsin.

Animals↗
PubMed1978

Endogenous prostaglandins and gastric secretion in the cat.

1. The gastric juice outputs of acid, pepsin, PGE and PGF, and the plasma concentrations of PGE and PGF have been measured in response to I.V. infusions of pentagastrin, histamine and insulin in the conscious cat. 2. There were significant correlations between the output of gastric acid and gastric outputs of both PGE and PGF during secretion produced by all stimulants. Furthermore, there were similar significant correlations between the gastric outputs of pepsin and both PGE and PGF. However, during insulin stimulation there was significantly more pepsin output per unit PGE or PGF output than during either pentagastrin or histamine stimulation. 3. The correlations between the outputs of gastric acid and both PGE and PGF were similar during pentagastrin and insulin stimulation whereas those between acid and PGE and PGF altered during the infusion of histamine. 4. It is concluded that these data partially, but not entirely, support the hypothesis that local release of prostaglandins may act as a negative feed-back mechanism on gastric acid secretion. 5. Plasma prostaglandin concentration did not correlate with changes in acid or pepsin secretion.

Animals↗
PubMed1978

Quantitation of somatostatin inhibition of insulin-stimulated gastric acid and pepsin secretion in the cat.

Somatostatin inhibition of gastric acid and pepsin secretion stimulated by insulin-hypoglycaemia was quantified in six conscious cats prepared with cannulated gastric fistulae. Somatostatin 0.5-5 microgram kg-1h-1 produced a dose dependent reduction of both acid and pepsin secretions stimulated by insulin 0.2 u kg-1h-1. The doses of somatostatin which produced 50% inhibition of pepsin and acid secretions (ID50) were not significantly different (0.70 +/- 0.16 and 0.93 +/- 0.11 microgram kg-1h-1 respectively). The slope of the calculated correlation line relating % inhibition of pepsin and % inhibition of acid is within experimental error of unity indicating equality of action of somatostatin on insulin-stimulated acid and pepsin secretion. The results indicate that somatostatin is a more potent inhibitor of insulin 0.2 u kg-1h-1 stimulated acid secretion than pentagastrin 8 microgram kg-1h-1 stimulated acid secretion, but is a more potent inhibitor of pentagastrin--than insulin--stimulated pepsin secretion. As insulin stimulates less acid and more pepsin secretion than pentagastrin, the differences in sensitivities to somatostatin of these secretions produced by the two stimulants is thought to be a result of the different absolute amounts of secretion produced by the stimulants.

Animals↗
PubMed1977

Comparison of vagal and meat stimulation on gastric acid secretion and serum gastrin.

The gastric acid secreted per unit of serum gastrin concentration or per unit of gastrin delivered to the gastric mucosa was significantly greater during electrical vagal stimulation than during stimulation by meat extract in the pyloric antrum. There was no significant difference in the concentrations of big, big gastrin or Components I and II in gastric venous serum during the two forms of stimulation. There were significantly greater concentrations of Components II and IV in gastric venous serum during meat extract stimulation than during vagal stimulation. The gastrin in gastric venous serum when meat extract was in the pyloric antrum was comprised of Component IV in addition to Component III whereas gastrin in extracts of cat antral mucosa was predominantly Component III. Gastric acid secretion in response to vagal stimulation was greater than can be accounted for by the action of gastrin alone and cannot be explained by differences in the known gastrin variants in the circulation during the two forms of stimulation.

Animals↗
PubMed1977

The effects of somatostatin and metiamide on tachyphylaxis of pentagastrin stimulated gastric acid and pepsin secretion in the conscious cat.

1. Pentagastrin stimulated gastric acid and pepsin secretions show parallel rates of tachyphylaxis in the conscious cat. The responses to histamine show only slight tachyphylaxis. 2. Somatostatin 10 microng.kg(-1).hr(-1) inhibits pentagastrin but not histamine stimulated acid secretion and inhibits pentagastrin stimulated pepsin secretion. 3. The inhibition of pentagastrin stimulated acid and pepsin secretion by Somatostatin delays the tachyphylaxis of these responses, but the rates of tachyphylaxis when they do subsequently occur are identical. 4. Metiamide 10 mg-kg(-1)-hr(-1) equally inhibits histamine and pentagastrin stimulated acid secretion but does not inhibit pentagastrin stimulated pepsin secretion. 5. Inhibiton of acid secretion during metiamide infusion neither prevents nor delays acid nor pepsin tachyphylaxis. 6. It is suggested that tachyphylaxis of acid and pepsin secretion is a gastrin receptor phenomenon and that Somatostatin occupies or modifies the behaviour of these receptors, preventing tachyphylaxis. Metiamide, however, exerts its action only on the histmine H2-receptor and not the gastrin receptor mechanism, and this apparently does not prevent or delay acid tachyphylaxis.

Animals↗
PubMed1977

Comparison of the effect of somatostatin on gastrointestinal function in the conscious and anaesthetized cat and on the isolated cat pancreas.

1. Somatostatin, 10 microgram kg-1 hr-1, inhibited gastric acid and pepsin secretion stimulated by pentagastrin, 8 microgram kg-1 hr-1, in conscious and anaesthetized cats with chronically implanted gastric fistulae. In the acutely surgically prepared anaesthetized cat, Somatostatin inhibited pepsin secretion but produced little inhibition of gastric acid secretion or mucosal blood flow. 2. Secretin stimulated pancreatic juice volume was not significantly reduced in acutely prepared anaesthetized cats, but there was a limited reduction of cholecystokinin-pancreozymin stimulated pancreatic amylase secretion and gall bladder contraction. 3. Somatostatin had neither stimulatory nor inhibitory effects on electrolyte and amylase secretion in the isolated saline-perfused cat pancreas. 4. The results suggest that some of the effects of Somatostatin may depend on the interaction on the target cell of other factors, nervous or humoral which may vary in different experimental preparations.

Amylases↗
PubMed1976

The pepsinogens of cat gastric mucosa and the pepsins derived from them.

Fundic mucosal extracts of the cat were examined by chromatography using DEAE-cellulose at pH 5.3. The peaks of proteolytic activity located by this method were shown to be heterogeneous on electrophoresis. By electrophoresis of individual homogenous chromatographic fractions 9 separate zones of proteolytic activity were detected. One zone did not migrate from the origin and is possibly a non-pepsinogen gastric protease. Simultaneous electrophoresis of pepsinogens and pepsins indicated that each pepsinogen gave rise to one pepsin. One zymogen gives rise to a pepsin active with the synthetic substrate acetyl-L-phenylalanyl-L-diiodotyrosine (APDT).

Animals↗
PubMed1976

Immunoreactive gastrin in differential and density gradient fractions of rat gastric mucosa.

Immunoreactive gastrin was measured in subcellular fractions of rat gastric mucosa. The sedimentational properties of subcellular gastrin-containing structures were distinct from those of mitochondria. After centrifugation in sucrose density gradients using a zonal rotor, the peak of immunoreactive gastrin was found in 1-17--1-18 g cm(-3) density sucrose (1-35 M; 39-5%, W/W). A thermolabile component with 125I-labelled gastrin-binding activity present in gastric mucosal homogenates and fractions was not associated with the gastrin storage vesicles sedimenting in density gradients.

Animals↗