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Biomedical subjects

K Ohata

Publications and source records attributed to K Ohata.

At least 109 records · Page 6Linked to original sources
PubMed1985

Studies on toluene diisocyanate (TDI)-induced delayed type hypersensitivity.

The toluene diisocyanate (TDI)-induced delayed type hypersensitivity reaction (DTH) in the ear of male mice was investigated and compared with the picryl chloride (PC)-induced one. The results obtained were as follows: 1) When 1% TDI solution (20 microliters/ear) as a challenging concentration was used for 7 weeks-old ICR mice, distinct ear swelling was observed in every group sensitized with various concentrations (1-5%, 100 microliters/animal) of TDI solution, and the swelling rate was the same or higher than that of PC-induced DTH. 2) Five, 7 and 13 weeks-old ICR mice showed a similar high response in TDI-induced DTH, whereas the reactivity of 16 weeks-old ICR mice was significantly lower than that of the above-mentioned younger mice. 3) In both TDI- and PC-induced DTH, ICR and BALB/c mice showed a similar high response, whereas the reactivity of ddY mice was significantly lower. The relationship between increase of the ear swelling and the amount of Evans' blue dye leaked being regarded as the intensity of its vasopermeability was also studied. The results obtained were as follows: 1) The dye leakage reached the maximum at 20 hr after challenge in sensitized mice. This peak preceded slightly that of the ear swelling (25 hr after challenge). 2) A positive correlation was observed between ear swelling and dye leakage (r = 0.87, P less than 0.01). The effects of dexamethasone (DX) and indomethacin (IM) were investigated with the TDI-induced DTH model. The DTH reaction was suppressed significantly by both drugs, but the suppressive effects of DX were higher than that of IM. All the above results indicate that the TDI-induced DTH model in mice taking dye leakage as an index may be useful for evaluation of drugs for disorders derived from DTH reactions.

Animals↗
PubMed1984

Comparison of kinins derived from rat stomach tissue and produced by catheptic enzyme in rat stomach.

Four uterine-contractile substances (a, b, c and d) and three uterine-contractile substances (a', c' and d') were obtained from the reaction mixture of rat plasma kininogen with the kinin-forming enzyme in rat stomach and the homogenate of the rat stomach with 0.2% acetic acid, respectively. By high performance liquid chromatography with a Zorbax ODS reversed-phase column, the retention times of materials a, c and d were found to be equal to those of materials a', c' and d', and they were not equal to those of kallidin, methionyl-lysyl-bradykinin (MLBK) and bradykinin (BK). The retention time of material b was equal to that of BK. The uterine-contractile activities of the materials a, b, c, d, a', c' and d' were all abolished by chymotrypsin, but not by trypsin treatment. These materials all relaxed the isolated rat duodenum in the presence of atropine, dibenamine, diphenhydramine and propranolol, and they produced a fall in rabbit blood pressure after administration of atropine, dibenamine and propranolol. The content ratios of a: b: c: d and a': c': d' were 4: 4: 67: 25 and 65: 19: 16, respectively, as calculated from the uterine-contractile activities of these materials.

Animals↗
PubMed1984

Receptor binding profile of quinupramine, a new tricyclic antidepressant.

The receptor binding profile, composed of the Ki-values measured in eight different receptor binding models using rat brain membranes, is reported for the new tricyclic antidepressant quinupramine, 10,11-dihydro-5-(3-quinuclidinyl)-5H-dibenz[b, f]azepine, and three reference compounds with a tertiaryamine side chain. Quinupramine was found to possess high affinity for muscarinic cholinergic and histamine H1 receptor binding sites in rat brain, whereas its affinity for imipramine binding sites was only one seventieth that of imipramine. Receptor binding profiles of the reference compounds were almost similar to that of quinupramine, except in the case of imipramine binding sites.

Animals↗
PubMed1984

Radioimmunoassay of guanabenz, an antihypertensive agent.

Antibodies with a high specificity and sensitivity for [(2,6-dichlorobenzylidene)amino]guanidine acetate (guanabenz, GB), a potent antihypertensive agent, were produced in rabbits immunized with GB conjugated to bovine serum albumin. GB-specific antibodies were detected 6-8 days after the first booster injection and the titer steadily increased over the initial 17-25 weeks of immunization. A high degree of specificity was demonstrated. No metabolite of GB detected in humans or several animal species cross-reacted, even when present in over 100-fold excess. A rapid and convenient radioimmunoassay procedure for GB was designed using these antibodies. Competition between tritiated GB tracer and unlabeled GB for specific antibody binding sites made feasible measurement of as little as 30 pg GB. GB was absorbed rapidly from the gastrointestinal tract and reached a maximum level in the plasma (2.50 +/- 0.45 ng/ml) at 2 h after oral administration (1 mg/kg) to dogs.

Animals↗
PubMed1983

Pharmacological activities of a kinin released from rat plasma by catheptic enzyme in rat stomach.

A kinin (material c), which was different from kallidin, methionyl-lysyl-bradykinin (MLBK), bradykinin (BK) and neurotensin, released from rat plasma by the kinin-forming enzyme in rat stomach was pharmacologically compared with BK and histamine or serotonin (5-HT) in various in vitro and in vivo systems. Material c produced contraction of isolated rat uterus, rat fundic strip, isolated guinea-pig ileum and guinea-pig tracheal chain; increased the vascular permeability of guinea-pig skin to circulating Evans blue; and produced a fall in rabbit blood pressure. Such effects were also produced by BK, but both were clearly discriminated by their quantitatively different activities. Histamine was not effective on isolated rat uterus, isolated rat duodenum, rat fundic strip, and rabbit blood pressure; produced contraction of isolated guinea-pig ileum and guinea-pig tracheal chain; and increased the vascular permeability of guinea-pig skin; but these activities were quantitatively different from those of material c. The contraction of isolated guinea-pig ileum elicited by histamine was sustained until it was removed from the bath, but those provoked by material c and BK gradually faded. 5-HT was qualitatively different from material c and BK with respect to contracting isolated rat duodenum. 5-HT also produced contraction of isolated rat uterus and rat fundic strip and produced a fall in rabbit blood pressure, but these activities were quantitatively different from those of material c and BK. As mentioned above, material c was quantitatively and qualitatively different from histamine and 5-HT.

Animals↗
PubMed1983

[Pharmacological studies of guanabenz. Effects on the peripheral nervous and other organ systems].

General pharmacological properties of guanabenz (GUB), a new anti-hypertensive agent, were studied in comparison with those of clonidine (CLD) and guanethidine (GUD). Intravenous or peroral administration of GUB caused a contraction of the nictitating membrane in cats and mydriasis in mice, while it produced an inhibitions of the gastrointestinal motility in dogs; the motility of isolated rabbit ileum; and chacol transport, salivation and gastric acid secretion in rats. GUB had no or slight inhibitory actions on contractile responses induced by peripheral sympathetic or parasympathetic nerve stimulation in various organs; however, it had antagonistic actions against the norepinephrine-induced contraction of isolated guinea-pig vas deferens. The contractile responses to epinephrine and tyramine in the nictitating membrane and to sympathetic nerve stimulation in isolated guinea-pig vas deferens were potentiated by GUB. GUB specifically antagonized the serotonin-induced contraction of the isolated rat fundus strip and nonspecifically inhibited acetylcholine, histamine or Ba2+-induced contractions of isolated guinea-pig ileum at higher concentrations. GUB exhibited local anesthetic actions and diuretic effects, but had no particular actions on neuromuscular transmission, isolated rat uterus, guinea-pig tracheal muscle and the hematic system. These effects of GUB were found to be almost identical with but less potent than those of CLD. The effects of GUD were basically different from GUB.

Animals↗
PubMed1982

[Studies on the antinociceptive activity of guanabenz, with particular reference to clonidine and morphine (author's transl)].

The antinociceptive activity of guanabenz, a new potent antihypertensive agent, and its interaction with alpha-adrenoceptors or opiate receptors, with particular reference to clonidine and morphine, were studied. Guanabenz, clonidine and morphine were found to possess a dose-dependent antinociceptive activity in mice and rats. In the tail flick assay, the antinociceptive activity of guanabenz and clonidine was antagonized by yohimbine but not by naloxone or phenoxybenzamine. Guanabenz, clonidine and morphine caused a concentration-dependent inhibition of the twitch response of transmurally stimulated guinea-pig ileum longitudinal muscle. Phentolamine and yohimbine reversed the twitch-inhibitory effects of guanabenz and clonidine, but naloxone failed to reverse this action. Guanabenz and low doses of clonidine caused locomotor hypoactivity. This action of both drugs was affected by yohimbine but not by phenoxybenzamine. In contrast, a high dose of clonidine caused locomotor hyperactivity which was affected by phenoxybenzamine but not by yohimbine. These results suggest that the antinociceptive activity of guanabenz, as in the case of clonidine, may be mediated by the activation of alpha 2-adrenoceptors and be independent from opiate receptors.

Analgesics↗
PubMed1982

Kinin formation by catheptic enzyme in rat stomach.

Four uterine-contractile substances (a, b, c and d) were extracted from procedures with acetic acid, n-butanol, distilled water, and methanol from the reaction mixture obtained by incubating rat plasma kininogen with the kininforming enzyme in the rat stomach. Gradient and equilibrium chromatography on SP-Sephadex C-25 columns were carried out with the extract containing these materials (a, b, c and d). The materials could not be separated by chromatography on SP-Sephadex C-25, but were separated by high performance liquid chromatography (HPLC) with a Zorbax ODS reversed-phase column. All the materials (a, b, c and d) contracted the rat uterus and relaxed the rat duodenum. The uterine-contractile activity of the materials was abolished by chymotrypsin, but not by trypsin treatment. The retention times of materials a, c and d on HPLC were different from that of kallidin, MLBK, bradykinin (BK) and neurotensin; but the retention time of material b was equal to that of BK. The content ratio of a: b: c: d was 4: 4: 67: 25, calculated from the uterine-contractile activity of these materials. The apparent molecular weight of the major material c, estimated by gel chromatography, was 1650. Material c contracted the rat uterus (1.2 x 10(-10) g/ml), relaxed the rat duodenum (2 x 10(-10) g/ml), and produced a fall in rabbit blood pressure (4.4 x 10(-8) g/kg). Material c was classified as a biologically BK-like peptide which is distinct from kallidin, MLBK, BK and neurotensin.

Animals↗