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Y Onoda

Publications and source records attributed to Y Onoda.

At least 19 recordsLinked to original sources
PubMed2001

KF31327, a new potent and selective inhibitor of cyclic nucleotide phosphodiesterase 5.

The effects of KF31327 (3-ethyl-8-[2-(4-hydroxymethylpiperidino)benzylamino]-2,3-dihydro-1H-imidazo[4,5-g]quinazoline-2-thione dihydrochloride) on phosphodiesterase 5 (cyclic GMP-specific phosphodiesterase) activity and platelet aggregation were investigated and compared with those of sildenafil, a well-known phosphodiesterase 5 inhibitor. KF31327 inhibited phosphodiesterase 5 from canine trachea (K(i)=0.16 nM) more potently than sildenafil (K(i)=7.2 nM). The kinetic analysis revealed that KF31327 was a non-competitive inhibitor. In the presence of nitroglycerin (nitric oxide generator), both compounds inhibited the collagen-induced aggregation of rabbit platelets at less than 0.1 microM, augmenting intracellular cyclic GMP level without affecting cyclic AMP. In contrast, in the absence of nitroglycerin, a higher concentration (10 microM) of KF31327 was required to inhibit platelet aggregation and increased both cyclic nucleotide levels. However, 10 microM sildenafil did not affect aggregation despite elevation of cyclic GMP comparable to that in the presence of nitroglycerin. These results indicate that in the presence of nitroglycerin, the inhibition of platelet aggregation by KF31327 is due to the elevation of cyclic GMP, whereas the mechanism underlying the inhibition without nitroglycerin might be related to a rise in intracellular cyclic AMP.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Duodenogastric reflux following cholecystectomy in the dog: role of antroduodenal motor function.

BACKGROUND: Duodenogastric reflux has been implicated in the pathogenesis of gastric ulcer and gastritis. Duodenogastric reflux after cholecystectomy is also a possible cause of post-cholecystectomy syndrome. AIM: To investigate the role of antroduodenal motor function in increased duodenogastric reflux following cholecystectomy and the effect of trimebutine maleate (trimebutine) on the duodenogastric reflux in conscious dogs. METHODS: Antropyloric and duodenal motility and bile acids content in the gastric juice were measured for 3 h during the inter-digestive state in dogs with or without cholecystectomy. RESULTS: Bile acids content in the gastric juice of cholecystectomized dogs was significantly higher than that of non-cholecystectomized dogs. The frequency of pyloric relaxation during phase II of the migrating motor complex was significantly increased following cholecystectomy. Intravenous infusion of trimebutine inhibited both the increased duodenogastric reflux and the frequency of pyloric relaxation in the cholecystectomized dog. CONCLUSION: Duodenogastric reflux and frequency of pyloric relaxations were increased in cholecystectomized dogs and trimebutine suppressed both of them. These findings suggest that the increased frequency of pyloric relaxation contributes to the duodenogastric reflux following cholecystectomy.

Animals↗
PubMed2001

Synthesis of optically active TAN-67, a highly selective delta opioid receptor agonist, and investigation of its pharmacological properties.

We have synthesized the nonpeptidic highly selective delta opioid receptor agonist, (+/-)-TAN-67, (4aS*, 12aR*)-4a-(3-hydroxyphenyl)-2-methyl-1,2,3,4,4a,5,12,12a-octahydropyrido [3,4-b] acridine. In spite of high potent agonist activity for the delta opioid receptor in in vitro assay, (+/-)-TAN-67 afforded no analgesic activity in the mouse warm-plate test. This result led us to separate (+/-)-TAN-67 into optically pure compounds. Each enantiomer of racemic TAN-67 was synthesized from the corresponding optically active 6-oxodecahydroisoquinoline which was obtained by fractional recrystallization of its optically pure di-p-toluoyl tartaric acid salt. In bioassay using mouse vas deferens, (-)-TAN-67 showed full agonist activity (IC50 = 3.65 nM). On the other hand, (+)-TAN-67 showed almost no agonist activity, but interestingly afforded hyperalgesic activity in vivo (i.t. injection).

Analgesics↗
PubMed1999

[Usefulness of pharmacokinetic modulating chemotherapy (PMC) for the postoperative adjuvant therapy of colorectal carcinoma: a preliminary report].

Pharmacokinetic modulating chemotherapy (PMC) using oral UFT and continuous venous 5-FU infusion was administered to 22 resectable patients with Dukes' B2-D colorectal carcinomas. The regimen was arranged as follows: Group A (n = 12) UFT 300-450 mg/day, 5 days a week and 5-FU 440-600 mg/m2/24 hr (750-1,000 mg/body/24 hr) once a week, Group B (n = 10), UFT less than 300 mg/day, 5 days a week, and/ or 5-FU less than 440 mg/m2/24 hr (750 mg/body/ 24 hr) once a week. The control group (Group C, n = 26) was selected at random from among non-PMC cases matched for other background factors and in which surgery had been performed during the past 4 years. Fifteen out of 26 patients in Group C were treated with 5-FU masked compounds orally. The cumulative 2 year recurrent rates of Groups A, B and C were 8.3%, 52.0% and 50.0%, respectively; the rate of Group A was significantly lower than that of Group B (p < 0.05). Four patients who suffered from PMC-related side effects of grade 1-2 wanted to decrease their dosage of UFT and/or 5-FU. They were registered in Group B. These results suggest that the regimen of Group A was advantageous in improving the prognosis after resection of Dukes' B2-D colorectal carcinoma.

Administration, Oral↗
PubMed1998

The effect of nociceptin, an endogenous ligand for the ORL1 receptor, on rat colonic contraction and transit.

To assess the role of ORL1 (opioid receptor-like 1) receptor in the bowel movement, we investigated the effect of nociceptin on colonic contraction and transit in rats. Nociceptin (0.1-100 nM) concentration-dependently caused an immediate tonic contraction followed by rhythmic waves of contractions in the isolated colon. The response to nociceptin (10 nM) was not affected by the classical opioid receptor antagonists, naloxone, naltrindole and nor-binaltorphimine. Suppression of effect of inhibitory neurotransmitters using pituitary adenylate cyclase activating polypeptide(6-38) (PACAP-(6-38); 3 microM), vasoactive intestinal polypeptide(10-28) (VIP-(10-28); 3 microM) and N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM) did not influence the nociceptin-induced contractions. In anesthetized rats, intravenous administration of nociceptin (1 microg/kg) or morphine (1 mg/kg) caused phasic contractions in the proximal colon. Pretreatment with naloxone (300 microg/kg, i.v.) abolished the contractions induced by morphine, but not by nociceptin. The rate of large intestinal transit was dose-dependently accelerated by nociceptin (0.03-3 microg/kg, s.c.), but was retarded by morphine (1.7-5 mg/kg, s.c.). These results indicate that stimulation of ORL1 receptor accelerates the colonic contraction and transit independently from opioid receptors.

Animals↗
PubMed1998

A study of the internal structure of the mandibular ramus in Japanese.

To clarify the internal structure of the mandibular ramus in Japanese adults, we performed bone morphometry. Specimens were obtained from four areas: the mid-area between the mandibular foramen and the lowest point of the mandibular notch, areas immediately above and below the mandibular foramen, and the mid-area between the mandibular foramen and the mandibular angle. The mandibular ramus was divided into the anterior and posterior parts, and morphometric analysis was performed on the four areas in each part. The percentage of the trabecular bone area in spongy bone was higher in the anterior part than in the posterior part. In both the anterior and posterior parts, the percentage of trabecular bone was the highest in the most inferior area. Trabecular bone was thicker in the anterior part than in the posterior part. Both in the anterior and posterior parts, trabecular bone was the thickest in the most inferior area. The arrangement of trabecular bone was more complicated in the anterior part than in the posterior part. Trabecular bone was most frequently arranged in the anteroposterior direction. In the superior area of the posterior part, much trabecular bone ran from the posterior buccal side toward the anterior lingual side. Compact bone was thicker in the anterior part than in the posterior part and on the buccal side than on the lingual side. No age-related changes were observed in any element of trabecular bone structure.

Aged↗
PubMed1997

Protection by histidine against oxidative inactivation of AMP deaminase in yeast.

Oxidative inactivation of AMP deaminase and its protection were analyzed under the in situ conditions of yeast cells. AMP deaminase was readily inactivated by an exposure to hydrogen peroxide plus copper in permeabilized yeast cells. Addition of ascorbic acid further enhanced the inactivation of the enzyme, suggesting the hydroxyl radical produced by the Fenton reaction is responsible for the inactivation of the enzyme. Addition of histidine caused an effective protection against the inactivation of AMP deaminase by hydrogen peroxide-induced hydroxyl radical. The concentration of histidine required for half-maximal effect was within physiological range. Cysteine showed less effective protection against oxidative inactivation. Other amino acids as potent copper-chelating agents as well as trolox and taurine showed little or no effect. Histidine can act as a physiological "antioxidant" in yeast cells.

AMP Deaminase↗
PubMed1993

Evidence that the enzyme catalyzing the conversion of guanosine diphosphate D-mannose to a 4-keto sugar nucleotide intermediate requires nicotinamide adenine dinucleotide phosphate.

The first enzyme in the formation of GDP-L-fucose from GDP-D-mannose, which forms a GDP-4-keto sugar intermediate, was purified to homogeneity from cell extracts of Klebsiella pneumoniae. During purification, the enzyme was found to be highly activated by NADP. It was proven that the pyridine nucleotide coenzyme of the enzyme was NADP, not NAD, which differs from previously accepted information. NAD had no effect on enzyme activity. The product of the enzyme reaction with NADP as coenzyme was separated from other nucleotides by high-performance liquid chromatography, and using ion spray liquid chromatography/mass spectrometry the mass was determined for the first time, as 587, which is same as the calculated mass of GDP-4-keto-6-deoxy-D-mannose.

Carbohydrate Dehydrogenases↗
PubMed1993

Effects of the new anti-ulcer drug ecabet sodium (TA-2711) on pepsin activity. I. Inactivation of enzyme protein.

To investigate the mechanism of the anti-peptic action of ecabet sodium (TA-2711) observed in pylorous-ligated rats, effects of this drug on the peptic activity of rat gastric juice, purified hog pepsin and pepsinogen were studied in vitro. After incubation with or without ecabet at acidic pH, the reaction mixture was centrifuged, and the peptic activity of the supernatant was measured. Ecabet depressed the peptic activity of pepsin and pepsinogen in parallel with a decrease in the protein concentration of the respective supernatant. Depression was greatest with pepsinogen (97% at 2.5 mg/ml of the drug) followed by gastric juice (about 60% at 10 mg/ml), and inhibition of the peptic activity of pepsin was weakest (about 10% at 10 mg/ml). When a fraction of the rat gastric juice containing substances with molecular weights below 10,000 was added to the pepsin solution, the anti-peptic activity of ecabet was potentiated. These results suggest that oral dosing of ecabet reduces the peptic activity of gastric juice by precipitating pepsin, which is facilitated by an unknown component(s) of gastric juice, and that the inactivation of pepsinogen may also contribute to the anti-peptic activity of ecabet.

Abietanes↗
PubMed1993

Effects of the new anti-ulcer drug ecabet sodium (TA-2711) on pepsin activity. II. Interaction with substrate protein.

To define the mechanism of the protection by ecabet (TA-2711) of the gastric mucosa from peptic attack, the characteristics of protein binding of this drug and its effect on peptic hydrolysis of substrate proteins were investigated in vitro. Both the binding to proteins and the hydrophobicity of ecabet were dependent on the pH; the lower the pH, the higher both parameters. The percentage of ecabet bound to proteins was nearly constant, being independent of the drug concentration at pH's below 2, indicating that this drug is bound to proteins in a non-specific manner. The activity of peptic hydrolysis of bovine serum albumin (BSA) decreased in the presence of ecabet, and this was not due to the interaction between pepsin and ecabet judging from the kinetic studies. The apparent Km values of peptic hydrolysis of BSA increased depending on the quantity of ecabet bound to BSA. These results suggest that ecabet is bound to substrate proteins by a non-specific hydrophobic interaction to form a complex that is less vulnerable to peptic hydrolysis.

Abietanes↗
PubMed1993

Comparison of the effects of T-1815, yohimbine and naloxone on mouse colonic propulsion.

The colonic prokinetic activity of a newly synthesized compound, T-1815, administered orally, was compared with that of yohimbine and naloxone in mice. The time required to evacuate a glass bead inserted into the distal colon was taken as an index of prokinetic activity. Clonidine (3-30 micrograms/kg s.c.), and loperamide (0.3-3.0 mg/kg s.c.) delayed bead expulsion in a dose-dependent manner. Yohimbine (0.3-10 mg/kg) and T-1815 (0.1-10 mg/kg) showed a dose-dependent reduction of the delay in evacuation induced by clonidine, but naloxone had no effect. The loperamide-induced retardation of colonic propulsion was reduced by naloxone (0.3-10 mg/kg) and T-1815 (0.1-10 mg/kg) in a dose-dependent manner, but yohimbine had no effect. In normal animals, yohimbine and naloxone had no significant effect on evacuation, while a slight acceleration was observed with T-1815 at 10 mg/kg. No soft feces and/or diarrhea were observed with any of the three test drugs. These results indicate that T-1815 appears to be a unique colonic prokinetic compound, the action of which may be mediated through mechanisms other than antagonism for alpha 2-adrenoceptors or opioid receptors.

Administration, Oral↗
PubMed1993

Effect of a new colonic prokinetic compound, T-1815, on gastrointestinal motility in anesthetized and conscious fasted dogs.

Effect of T-1815, a new colonic prokinetic compound, on gastrointestinal motility was studied in anesthetized and conscious dogs fasted for 24 hr before experiment. In anesthetized dogs, intravenous injection of T-1815 in doses of 0.3-3.0 mg/kg caused a biphasic effect on the gastric motility, a slight decrease followed by a slight increase. While the compound elicited only an increase in motility of the duodenum, jejunum and colon. In the colon, high-amplitude contractions were observed in 2 out of 5 animals at 1 mg/kg, i.v. of T-1815 and 4 out of 5 animals at 3 mg/kg. Bethanechol at 0.01 mg/kg, i.v. produced only a potentiation of the motility in all of the sites, but never induced high-amplitude contractions in the colon. During the interdigestive state in conscious dogs, intravenous T-1815 at 1 and 3 mg/kg caused contractions similar to the interdigestive phase III contractions at the stomach and duodenum in only 2 out of 7 experiments, and colonic motility was slightly depressed at 3 mg/kg. Oral administration of T-1815 at 30 and 50 mg/kg did not elicit the phase III-like contractions but produced persistent contractions at the stomach and duodenum in 2 out of 4 conscious animals during the interdigestive state. In the proximal and middle colon, high-amplitude contractions were observed in 5 out of 7 animals by 10-50 mg/kg, p.o. of T-1815. From the above results, it is concluded that the pharmacological effect of T-1815 on gastrointestinal motility is different from that of the cholinergic agonist. In addition, T-1815 seems to have a characteristic to induce high-amplitude contractions which are known to be closely related to defecation.

Administration, Oral↗
PubMed1992

[Effects of trimebutine on colonic propulsion in mice].

Effects of oral administration of trimebutine on colonic propulsion in conscious mice were studied by measuring the time required to evacuate a bead which had been inserted into the colon, and compared with those of metoclopramide and domperidone. In normal animals, trimebutine (10 and 50 mg/kg), metoclopramide (50 mg/kg) and domperidone (50 mg/kg) had no effect on the bead evacuation. Metoclopramide and domperidone at 30 mg/kg showed no effect on the delay of colonic propulsion induced by clonidine, while trimebutine (10 and 30 mg/kg) restored the delay significantly. Trimebutine also showed restoration of the delay induced by loperamide. On the acceleration of the propulsion induced by neostigmine, trimebutine (10 and 30 mg/kg) showed an inhibition. In addition, trimebutine (3-30 mg/kg) dose-dependently suppressed the development of soft feces and/or diarrhea induced by neostigmine. According to the results, it is concluded that trimebutine produces both acceleration and inhibition on the colonic propulsion in mice.

Administration, Oral↗
PubMed1992

A study of the internal structure of the Japanese mandible.

The thickness of the substantia compacta and the volume and width of the trabecular bone of the substantia spongiosa were investigated by soft X-ray photographs made of thin sections of many kinds of dentulous and edentulous mandibles. The results were: 1) The thickness of substantia compacta is especially thick on the lingual side in the incisor region and thickest in the molar region in all materials. At the base of mandible, the thickness is essentially the same in all regions, but, the thickness of dentulous materials is greater than of edentulous ones. 2) On the upper part, the volume of trabecular bone is less in the premolar region in both edentulous and dentulous material than in other regions, however, there is relative more in edentulous than in dentulous. In the central part, there is almost the same amount of trabecular bone in the dentulous and edentulous material. 3) The width of the trabecular bone in the substantia spongiosa is greater in the incisor region than in other regions in all materials. In the upper and central part, it is smaller in the premolar region in both edentulous and dentulous material but, it increases in the molar region in the edentulous materials.

Adult↗
PubMed1991

Effects of the new anti-ulcer agent 12-sulfodehydroabietic acid monosodium salt on healing of acetic acid-induced gastric ulcers in rats.

The macroscopic and microscopic effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711, CAS 86408-72-2) on the healing of acetic acid-induced gastric ulcers in rats were compared with those of sucralfate and carbenoxolone. Test compounds were given orally twice a day for 10 consecutive days from the day after the injury with glacial acetic acid. TA-2711 (50 and 100 mg/kg) dose-dependently decreased the macroscopic ulcer index (mm2). In addition, at a dose of 100 mg/kg, this drug decreased the length of mucosal defect in the ulcerated region and increased the mucosal regeneration index estimated by microscopic observation. Furthermore, the mucosa surrounding the ulcerated area and the regenerated epithelium in the TA-2711 administered group contained more PAS (periodic acid-Schiff)-positive material than those in the control group. On the other hand, neither sucralfate nor carbenoxolone (100 mg/kg) showed any significant effects on ulcer healing.

Abietanes↗
PubMed1990

Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric mucosal lesions induced by necrotizing agents and gastric mucosal defensive factors in rats.

Effects of TA-2711 on gastric mucosal lesions induced by various necrotizing agents and several defensive factors of gastric mucosa were investigated in rats. Oral administration of TA-2711 at 12.5 to 200 mg/kg prevented the formation of gastric mucosal lesions induced by 99.5% ethanol, 0.6 N HCl, 0.2 N NaOH and boiling water with ED50 values of 24, 58, 16 and 101 mg/kg, respectively. Oral TA-2711 at 100 mg/kg increased the gastric mucosal prostaglandin E2 (PGE2) level without any change in transmucosal potential difference. A sustained decrease in gastric mucosal blood flow produced by intragastric administration of 99.5% ethanol was inhibited by oral TA-2711 (50, 100 mg/kg) and 16,16-dimethyl PGE2 (10 micrograms/kg). The effect of TA-2711 on ethanol-induced decrease in blood flow was suppressed by indomethacin (10 mg/kg, s.c.). Oral TA-2711 (25-100 mg/kg) dose-dependently increased the amount of mucus adherent to the gastric mucosa. In addition, gastric HCO3- secretion was increased by intragastric TA-2711 at 2.5 and 5.0 mg/ml. These results suggest that TA-2711 enhances gastric mucosal resistance by increasing mucus and HCO3- secretion and by maintaining mucosal blood flow, and protects the gastric mucosa against various irritants. The effects of TA-2711 appear to be mediated by mucosal prostaglandins such as PGE2.

Abietanes↗