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M Moriga

Publications and source records attributed to M Moriga.

At least 55 records · Page 3Linked to original sources

Studies on peptides. CXI. Synthesis of chicken gastrin-releasing peptide.

The heptacosapeptide amide corresponding to the entire amino acid sequence of chicken gastrin-releasing peptide (cGRP) was synthesized similarly to the synthesis of porcine GRP by assembling six peptide fragments followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole in TFA. A new carboxyl-activating reagent, thiazolidine-2-thione, was preferentially adopted for preparation of necessary fragments. The synthetic cGRP, purified by ion-exchange chromatography, followed by partition chromatography, was active as the synthetic porcine GRP, when plasma immunoreactive gastrin level was examined in rats. No obvious difference was observed when synthetic and natural cGRP preparations were compared by HPLC, immunochemical property and biological activity in dogs.

Amino Acid Sequence↗

Effect of topical application of amino acids on gastric pepsin secretion in the rat.

The effect of amino acids and other chemicals of intragastric perfusion on pepsin secretion was studied in anaesthetized rats. Irrigation of the stomach with glycine caused concentration-dependent increase in pepsin output, but not in acid output. Pepsin stimulatory effect was decreased by an increase of the carbon chain between the amino group and carboxyl group of glycine and by transposing the amino group from alpha- to gamma-position in amino-n-butyric acid. Acidification of perfusate, a local irrigation of lidocaine and an intravenous infusion of atropine reduced but did not abolish the pepsin response to chemical stimulation. Since serum gastrin level was not changed from basal levels during pepsin secretion induced by amino acids, the mechanism of chemical stimulation appears to be gastrin-independent. The comparison of the secretagogue activity of amino acids shows that glycine exhibited the strongest stimulation of pepsin output, reaching 208% of the response to tetragastrin at the dose of 8 microgram/kg/hour. All other amino acids tested were found to stimulate pepsin secretion, whereas bovine serum albumin and hydrochloric acid were inert in this respect. The result indicates that the chemical stimulation of the stomach by amino acids is capable of inducing pepsin secretion by a local, gastrin-independent mechanism sensitive to pH and related to the molecular configuration of amino acids.

Amino Acids↗

Effect of topical application of amino acids on gastric pepsin secretion in the rat. Part II: effect of pH changes and glycine in separate perfusion preparation.

Gastric acid and pepsin were measured in antrum and fundus separately by perfusing each region of the stomach in anaesthetized rats. Perfusion of the antral region with alkaline and acid solutions did not affect gastric acid and pepsin secretions in the fundic gland region. Gastric secretions in the antrum and acid secretions in the fundus remained unchanged when each region of the stomach was instillated with glycine. Pepsin stimulation was observed in the fundic region only when perfused with glycine. We confirmed our previous observation that topical amino acid in the oxyntic gland stimulated pepsin secretion directly. The pepsin stimulatory effect of amino acid was found to be independent of antral regulation.

Administration, Topical↗

Effect of topical application of amino acids on gastric pepsin secretion in the rat. Part III: effect of L- and D-isomers of amino acids on gastric secretion in reperfusion system.

This study was undertaken to compare the potency of each L- and D-isomers of 5 amino acids in stimulating gastric acid and pepsin secretion by the intragastric reperfusion preparation in rats. Gastric basal and glycine-stimulated secretions in this preparation were lower than those Ghosh-Lai preparation, but not to a statistically significant extent. All D- and L-isomers of amino acids tested were found to markedly stimulate pepsin secretion, but to only slightly stimulate acid secretion. Pepsin stimulatory response to each D and L-isomer of amino acid was similar. The stimulatory effects of amino acids thus seem to be unrelated to the optical stereoisomeric configuration.

Administration, Topical↗

Studies on peptides. CII. Synthesis of a heptacosapeptide amide corresponding to the entire amino acid sequence of gastrin-releasing peptide.

The heptacosapeptide amide corresponding to the entire amino acid sequence of gastrin-releasing peptide (GRP) was synthesized by assembling seven peptide fragments followed by deprotection with a new reagent system, IM trifluoromethanesulfonic acid-thioanisole in TFA. The deprotected peptide was purified by ion-exchange chromatography on CM-cellulose followed by partition chromatography on Sephadex G-25. The latter was found to remove effectively the Met (O) derivative of GRP. The highly purified synthetic GRP was active as synthetic bombesin on the molar basis. A new carboxyl-activating reagent, thiazoline-2-thione, was employed for preparation of the necessary fragments.

Amino Acid Sequence↗

The role of gastric mucosal hexosamine in aspirin-induced ulcers.

In order to elucidate the role of gastric tissue hexosamine, used as an index of mucopolysaccharide content, in the development and healing process of peptic ulcers, the distribution of hexosamine and the changes of gastric hexosamine content in the development and healing of aspirin-induced ulcers in rats were studied. In addition, the effects of proglumide and L-glutamine on gastric hexosamine were also studied. The hexosamine content was found to be the highest in the antrum, followed by the corpus and then the forestomach. The mucosa contained significantly higher hexosamine than the smooth muscle layer in both the antrum and the corpus. Prior treatment with proglumide significantly increased the mucosal hexosamine to the extent of 10.3--18.1% in the glandular stomach. Administration of aspirin decreased the gastric mucosal hexosamine and induced the onset of ulcer, while administration of proglumide suppressed the gastric lesions in proportion to dosage and correspondingly prevented a decrease of the hexosamine. In contrast, L-glutamine showed an anti-ulcerogenic effect without suppressing a decrease of the hexosamine. In the process of curing gastric lesions, proglumide accelerated the healing of the ulcers and simultaneously returned the total hexosamine content to its original level. These results suggest that the gastric mucosal hexosamine is closely related to the onset and healing of aspirin-induced ulcer in rats, and that proglumide contributes to both the prevention and healing of ulcers by increasing gastric mucosal hexosamine.

Animals↗

The activity of N-acetylglucosamine kinase in rat gastric mucosa.

The activity of N-acetylglucosamine kinase in the rat glandular stomach was studied to elucidate its participation in aspirin-induced ulcers, and the effect of proglumide, an anti-ulcer agent which was found to increase gastric mucosal hexosamine, on this enzymatic activity was also studied. N-Acetylglucosamine kinase activity was found to be significantly higher in the antrum than in the corpus, the antrum being 1.3--1.9 times as active as the corpus. The mucosal layer itself was about 1.8--2.0 times as active as the whole tissue of the glandular stomach. This enzymatic activity in the glandular stomach was found to decrease slightly after fasting and to further decrease after intragastric administration of aspirin (100 mg/kg). The pylorus-ligated rats showed a significant decline of this enzymatic activity following the administration of aspirin. Acceleration of N-acetylglucosamine kinase activity with proglumide was demonstrated in vivo and in vitro experiments. Prior treatment with proglumide prevented aspirin-induced ulcers and correspondingly stimulated this enzymatic activity. These results suggest that the activity of N-acetylglucosamine kinase in the rat glandular stomach closely parallels the distribution and localization of gastric hexosamine, glycosaminoglycans, and glycoproteins. A decrease of this enzymatic activity correlates with the production of ulcers by aspirin. The mechanism by which proglumide increases gastric hexosamine is at least partly attributed to the activation of N-acetylglucosamine kinase in the glandular stomach.

Animals↗

New device for the measurement of hydrogen clearance rate from the gastric mucosa.

The hydrogen clearance rate of the nucosa of the glandular stomach of the anesthetized rat was obtained with the platinum electrode in contact with the surface of the gastric mucosa (Contact Electrode Method). By using two indicator electrodes, the gastric blood flow was measured simultaneously with one electrode in contact with the mucosal surface (Contact Electrode Method), and with the other electrode inserted into the gastric wall (Inserted Electrode Method). Pentagastrin produced increase in blood flow by both contact and inserted electrode methods. Isoproterenol stimulated blood flow as determined by the contact electrode method, but when the flow was determined by the inserted electrode method it reduced the blood flow. The combination of these two methods is useful in the determination of the blood flow in the different layers of the stomach.

Animals↗

Effect of intravenous infusion of somatostatin on gastric, pancreatic and biliary secretion in the rat.

The effect of somatostatin (GH-RIH) on gastric, pancreatic and biliary secretion was examined in the anesthetized rats. Intravenous infusion of the hormone, in graded doses ranging from 1 to 16 microgram/kg/hr, produced a dose dependent inhibition of pentagastrin, 1.5 microgram/kg/hr, induced acid secretion, reaching about 54% of control level at the dose of 16 microgram/kg/hr. Somatostatin, 4, 16 and 64 microgram/kg/hr, inhibited the pancreatic juice volume stimulated by intravenous injection of secretin, 1 u/kg, as a bolus. Somatostastin, 2, 8, 32 and 128 microgram/kg/30 min, did not change the bile flow rate in control period. Somatostatin may play a physiological role in the regulation of the secretory process of the stomach and pancreas.

Animals↗

Studies on the pepsinogens of human gastric mucosal extracts.

1. Electrophoretic separation of proteases from human gastric mucosal extracts of five patients with gastric ulcer, one with duodenal ulcer and three with gastric cancer were investigated by agar-gel electrophoresis at pH 8.3 and pH 5.0. 2. In the fundic mucosal study, there were seven faster moving proteases in all nine cases, but the slowest moving protease showed a slightly different picture in each case. In the antral mucosal study, two of eight cases showed mainly group II pepsinogens, seven of nine cases, however, showed the same results as in the fundic mucosal study. 3. In the cases of the nine mucosal extracts activated at pH 1.5 or pH 4.0, they all showed the same electrophoretic separation at each pH level. At these two pH levels, however, quite different electrophoretic patterns were observed. The presence of pepsin 3 appeared to diminish at the higher levels of pH, although that of pepsin 5 and pepsin 7 appeared to increase at pH 4.0 and above. Pepsin 6 appeared for the first time at pH 4.0 and existed at higher pH levels. 4. We thus conclude that electrophoretic patterns of pepsins in the gastric mucosal extracts are changeable depending on the pH level of the incubating medium, and further that diversity of pepsins in gastric juices may also depend on the pH level of gastric juices.

Adult↗

Rat gastric secretion studies with synthetic gastrin-like tetrapeptide.

Gastric acid and pepsin secretions were measured in the perfusing rat stomach preparation with sodium-citrate-phosphate buffer, pH 6.6. In anesthetized rat stomach preparation, acid output in both basal and stimulated conditions seemed to be small, but pepsin output was observed even in a short period. In the rats which were fed freely just before use, basal pepsin output was significantly lower than that of fasted rats, although in the basal acid output and in the acid and pepsin output during stimulation in both groups, there was no difference statistically. Intravenous infusion of tetragastrin (1, 2, 4, 8, 16 and 32 microgram/kg/hr) produced a dose dependent acid and pepsin secretions. Tetragastrin, at the dose of 8 microgram/kg/hr, stimulated acid and pepsin output. Acid output was kept constant for three hours, but pepsin output was made to peak within an hour and formed a plateau after 1.5 hours at a level of 30% of peak pepsin output.

Animals↗