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Biomedical subjects

Y Hatanaka

Publications and source records attributed to Y Hatanaka.

At least 145 records · Page 8Linked to original sources
PubMed1987

Solubilization of porcine zonae pellucidae by trypsin and pronase.

The porcine zona pellucida was dissolved with difficulty by trypsin in isotonic solution, whereas it was efficiently dissolved by pronase. A structural change of the zona was induced in hypotonic solution, resulting in acceleration of dissolution by these proteases. The solubilization rate of three families (PZP1-3) of zona protein by both enzymes was analyzed by HPLC. In hypotonic solution, PZP1 was solubilized first, followed by PZP2; and PZP3 was then finally released. In isotonic solution, PZP1 and PZP2 were also solubilized faster than PZP3, which was almost completely resistant to trypsin, showing that the solubilization of the zona depended on that of PZP3. Noticeably, high molecular weight products were produced as the proteolytic hydrolysis proceeded in PBS. Circular dichroic spectra and electrophoretograms of the tryptic hydrolysates showed that the zona may have a regular supramolecular structure.

Animals↗
PubMed1985

Interactions of derivatives of guanidinophenylalanine and guanidinophenylglycine with Streptomyces griseus trypsin.

The rates of hydrolysis of the ester, amide and anilide substrates of p-guanidino-L-phenylalanine (GPA) by Streptomyces griseus trypsin (S. griseus trypsin) were compared with those of arginine (Arg) substrates. The specificity constant (kcat/km) for the hydrolysis of GPA substrates by the enzyme was 2-3-times lower than that for arginine substrates. The kcat and Km values for the hydrolysis of N alpha-benzoyl-p-guanidino-L-phenylalanine ethyl ester (Bz-GPA-OEt) by S. griseus trypsin are in the same order of magnitude as those of N alpha-benzoyl-L-arginine ethyl ester (Bz-Arg-OEt), although both values for the former when hydrolyzed by bovine trypsin are higher by one order of magnitude than those for the latter. The specificity constant for the hydrolysis of Bz-GPA-OEt by S. griseus trypsin is much higher than that for N alpha-benzoyl-p-guanidino-L-phenylglycine ethyl ester (Bz-GPG-OEt). As with the kinetic behavior of bovine trypsin, low values in Km and kcat were observed for the hydrolysis of amide and anilide substrates of GPA by S. griseus trypsin compared with those of arginine substrates. The rates of hydrolysis of GPA and arginine substrates by S. griseus trypsin are about 2- to 62-times higher than those obtained by bovine trypsin. Substrate activation was observed with S. griseus trypsin in the hydrolysis of Bz-GPA-OEt as well as Bz-Arg-OEt, whereas substrate inhibition was observed in three kinds of N alpha-protected anilide substrates of GPA and arginine. In contrast, no activation by the amide substrate of GPA could be detected with this enzyme.

Guanidines↗
PubMed1985

A new beta-naphthylamide substrate of p-guanidino-L-phenylalanine for trypsin and related enzymes.

N alpha-Benzyloxycarbonyl-p-guanidino-L-phenylalanine beta-naphthylamide (Z-GPA-beta NA) was synthesized and the susceptibility of this compound to trypsin and related enzymes was compared with that of N alpha-benzyloxycarbonyl-L-arginine beta-naphthylamide (Z-Arg-beta NA). Both Z-GPA-beta NA and Z-Arg-beta NA were rapidly and almost completely hydrolyzed by trypsin and pronase. Z-Arg-beta NA was hydrolyzed slowly by thrombin, while Z-GPA-beta NA was not susceptible to this enzyme at all. The rate of hydrolysis of Z-GPA-beta NA by papain was slower than that of Z-Arg-beta NA. Neither beta-naphthylamide substrate was hydrolyzed by alpha-chymotrypsin. The specificity constant (kcat/Km) for the hydrolysis of Z-GPA-beta NA by trypsin was somewhat larger than that for the hydrolysis of Z-Arg-beta NA. Contributions of the benzene ring in the side chain of Z-GPA-beta NA to good binding of this substrate to the specificity site of this enzyme and to the poor fit of the scissile bond in the substrate molecule to the active serine residue are presumed from comparison of the individual kinetic parameters (Km and kcat) for the two beta-naphthylamide substrates. Z-GPA-beta NA was ascertained to be a useful substrate in the study of the binding and catalytic specificities of various trypsin-like enzymes.

Benzoylarginine-2-Naphthylamide↗
PubMed1985

[Pharmacological actions of iprazochrome on the vascular system].

The pharmacological actions of iprazochrome (IC) on the vascular system were studied, and the following results were obtained: No death nor abnormal behaviors were observed in acute toxicity tests conducted on male and female mice and rats despite the administration of large doses of IC (10,000 mg/kg, p.o. and 80 mg/kg, i.v., respectively). IC inhibited dose-dependently platelet aggregation in vitro induced by arachidonate and ADP, whereas no effect was observed on ADP-induced respiratory depression in mice, which is closely related to platelet aggregation in vivo. The antiserotonergic actions of IC on the isolated external carotid arteries and femoral arteries in dogs observed in a noncompetitive manner were found to be 1/24 to 1/65 that of methysergide. On the other hand, IC showed no inhibitory effect on the paw edema of rats in vivo induced by serotonin. The inhibitory effect of IC on peritoneal dye leakage in mice was less than half that of phenylbutazone. IC prevented apoplexy in stroke-prone SHR (SHRSP) without lowering the blood pressure. Histological changes in the cerebrum of SHRSP were ischemic changes such as swelling of the neurons and shrinkage of the nuclei, mainly in the cerebral cortex and corpus striatum area.

Adrenochrome↗
PubMed1983

Hydrolysis of phenylthiazolones of p-guanidinophenylalanine and arginine by trypsin and related enzymes.

The phenylthiazolone (PTA) of p-guanidinophenylalanine (GPA) was synthesized and the susceptibility of this compound to trypsin and related enzymes was compared with that of the PTA of arginine (Arg). Both PTA-GPA and PTA-Arg were almost completely and rapidly hydrolyzed by trypsin and pronase. PTA-Arg was hydrolyzed rapidly by thrombin, whereas PTA-GPA was less susceptible to this enzyme. The rates of hydrolysis of the two PTAs by alpha-chymotrypsin and papain were fairly slow. The specificity constant (kcat/Km) for the hydrolysis of PTA-GPA by trypsin was about 4 times larger than that of PTA-Arg. Thus, PTA-GPA, as well as PTA-Arg, behaves as a specific internal thioester substrate for trypsin and is the best one in the series of PTA substrates examined so far. However, PTA derivatives of GPA and Arg were hydrolyzed with kcat/Km values smaller than those of N alpha-benzoyl ethyl esters of L-GPA and L-Arg by factors of 4 and 17, respectively.

Arginine↗
PubMed1982

[Effects of dihydroergotamine mesylate (DEM) on the cardiovascular and nervous systems (author's transl)].

Effects of DEM on the cardiovascular, autonomic, and central nervous systems were studied using dogs, rats and rabbits. DEM showed relatively weak effects on the EEG in curarized rabbits and on ambulatory and drinking activities in rats. DEM suppressed dose-dependently the pressor responses induced by norepinephrine, serotonin and bilateral carotid occlusion, but had no effect on the depressor responses induced by acetylcholine and electrical stimulation to the postganglionic vagus nerve in anesthetized dogs. DEM produced a dose-dependent increase in blood pressure, a dose-dependent decrease in heart rate, a transient decrease in respiration rate, and little change in the ECG of anesthetized dogs. The pressor responses induced by DEM were inhibited by phentolamine, methysergide, and indomethacin in anesthetized dogs. With canine femoral arteries, DEM-induced contractions were blocked 10% by phentolamine, 60% by methysergide, and enhanced 10% by indomethacin. On the other hand, DEM-induced contractions of the femoral veins were blocked 30% by phentolamine, 60% by indomethacin, and 10% by methysergide. DEM provoked a significant increase in the level of prostaglandin E in the bathing fluid of the veins but not in that of the arteries. The results suggest that the arterioconstrictor responses induced by DEM are mediated mainly through the serotonin receptors, and the venoconstrictor responses induced by DEM mainly through the enhanced synthesis of prostaglandin E.

Animals↗
PubMed1981

[Comparative responsiveness of isolated saphenous, femoral and external carotid arteries and veins of dogs to dihydroergotamine mesylate (DEM) (author's transl)].

Changes in tension of spiral strips of saphenous, femoral and external carotid arteries and veins were measured isometrically. DEM stimulated 6 preparations in almost the same concentration ranges (pD2 values were 8.64 to 8.40). However, the dose-response curves for DEM indicted variations in responsiveness among the different arteries and veins. Compared with norepinephrine (NE) (1)( the intrinsic activity of DEM was 0.002 on saphenous arteries, 0.05 on saphenous veins, 0.03 on femoral arteries, 0.18 on femoral veins, 0.13 on external carotid arteries and 0.13 on external carotid jugular veins. Thus DEM contracted more potently the venous strips from the hind limbs. IN femoral and external carotid arteries, antagonism of serotonin by DEM or methysergide was investigated. DEM displaced the dose-contractile response curves for serotonin in a noncompetitive manner, and the antagonistic response of DEM to serotonin was about 8 times more effective in external carotid arteries (pD'2 value=6.96) than in femoral arteries (pD'2 value=6.05). Methysergide, unlike DEM, antagonized the response to serotonin in a competitive manner at low doses but in a noncompetitive manner in high doses, and was fairly equal in antagonizing response to serotonin in external carotid arteries (pA2 value=that the therapeutic value of DEM in the treatment of orthostatic hypotension is due to its selective anti-serotonin activity on the external carotid arteries.

Animals↗
PubMed1980

A method for evaluating analgesic agents in rats.

A method is described for evaluating antinociceptive activity in rats using writhing responses induced by 4% sodium chloride solution. Narcotic and nonnarcotic analgesics, narcotic antagonists except naloxone, and antipyretic and nonsteroidal antiinflammatory drugs were effectively evaluated at relatively low doses using this method. Parenteral ED50 values of these compounds ran parallel to their clinical doses. The method detected not only the analgesic action of the above drugs but also that of methamphetamine. In spite of its high sensitivity, the method was specific in the sense that CNS-depressant, muscle relaxant, anticholinergic, and antihistamine drugs and anesthetics were inactive even at toxic doses. On the other hand, the decrease in the analgesic activity of morphine upon chronic injection was also observed with this method. The writhing test with 4% sodium chloride in rats was concluded to be a sensitive and specific test for analgesic drugs and useful for examining changes in analgesic activity of drugs during chronic administration.

Acetates↗
PubMed1980

Low tumor incidence in rats with long-term feeding of fusarenon-X, a cytotoxic trichothecene produced by Fusarium nivale.

In order to examine tumorigenic effects of fusarenon-X, a trichothecene compound produced by Fusarium nivale, feeding experiments on 151 male Donryu rats were carried out. Daily dose of 105 micrograms (7 ppm in the diet) or 50 micrograms (3.5 ppm)/animal of fusarenon-X was given for 1 or 2 years. Although the animals of the experimental groups showed lower body weight than controls and were more liable to be afflicted by pulmonary infections, tumor incidences were as low as that of the control group. However, several unusual tumors as follows were observed only in the experimental groups: 1 adenocarcinoma of the stomach, 2 papillary carcinomas of the urinary bladder, 1 adrenocortical adenoma, and 1 leukemia.

Animal Feed↗
PubMed1978

[The study of developmental pharmacology (I). Effect of pentazocine HCl on the physiology of rats given the drug during perinatal and postnatal periods (author's transl)].

The effects of drug administration on the dams (F0) and their offspring (F1), particularly on the central nervous and reproductive functions of F1, were studied by oral administration of pentazocine HCl to rats during the perinatal and postnatal periods. No significant differences were observed between administered and control rats regarding body weight changes and food intake during perinatal and postnatal periods in F0 at all dosages, but temporary salivation was observed in the 200 and 100 mg/kg groups, and decline of spontaneous activity and respiratory rate, disappearance of righting reflex, clonic convulsion were observed in some of the 200 mg/kg group. No significant differences were observed regarding litter size, birth rate, state and timing of differentiation as postnatal development, sex maturity, reproductive function in F1, although some groups were slightly inferior in body weight at birth and during the nursing period. Furthermore, no differences were observed in respect to the nervous functions of balance, exercise and psychotic related activity in the open-field test.

Administration, Oral↗