Studies on coumarins of a Chinese drug "qian-hu"; VII. Structures of new coumarin-glycosides of zi-hua qian-hu and effect of coumarin-glycosides on human platelet aggregation.
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Biomedical subjects
Publications and source records attributed to S Shibata.
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A case of two tumors arising in an endometriotic cyst of the ovary is described. These two tumors are macroscopically polypous and are histologically a clear cell carcinoma and an endometrioid carcinoma, respectively. This is a rare neoplasm and its existence supports the general opinion that clear cell carcinoma and endometrioid carcinoma of the ovary are both müllerian in origin.
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Passive Heymann nephritis with acute and severe proteinuria was produced in rats by a single injection of heterologous antibody against a purified glycoprotein which consisted of homologous subunits with a molecular weight of 108,000 (gp108). Gp108 was identified as one of the major antigens in rat renal tubular fraction (FX1A) on immunoblotting assay by using total proteins of FX1A and rabbit antiserum against FX1A. A band of gp330, which was identified as a pathogenic antigen of Heymann nephritis by Kerjaschki D and Farquhar MG (Proc Natl Acad Sci USA 79:5557, 1982) was detected as another band by Coomassie blue staining and immunoblotting. Autoantibodies in the sera of FX1A-injected (active Heymann nephritis) rats reacted to the band of gp330 but not to gp108. These results indicate that gp108 is a different glycoprotein from both gp330 and its degradation products. GP108 was subsequently purified to near homogeneity by extraction with Triton X-100, and then DEAE-cellulose and Bio-Gel A-1.5m column chromatographies. On gel permeation chromatography, the purified antigen showed a molecular weight of 310,000, suggesting that it consists of dimer or trimer of gp108. Rabbits immunized with gp108 produced an antibody which showed monospecific binding to gp108. The antibody stained with brush border of proximal renal tubules in addition to the capillary loops in rat glomeruli by indirect immunofluorescence. Injection of rabbit antiserum against gp108 in rats induced severe proteinuria within 2 days. On the 2nd day after the injection, the glomeruli of the animals showed granular immune deposits along the capillary loops in addition to dominant staining of the brush border of the proximal tubules by immunofluorescence. These results indicate that gp108 is a pathogenic antigen in passive Heymann nephritis and that an antibody against gp108 has a nephritogenic and proteinuria-inducing activity.
The intracellular oxygen tension in hamster embryos at various early stages of development was examined using a microelectrode technique. Changes in PO2 values before and after insemination in vitro were also investigated. The results were as follows. The oxygen tension in the culture medium was 83.8-99.0 mmHg. On the other hand, the mean oxygen tension in unfertilized oocytes was 51.1 +/- 7.3 mmHg (range 38.0-63.8 mmHg) and remained at these unfertilized levels throughout fertilization (49.6 +/- 7.1 mmHg). Slight but significant increases in oxygen tension in embryos occurred at the 2 cell stage and each successive stage. Mean values for PO2 in 2 cell, 4 cell and 6-8 cell stages were 58.5 +/- 5.6, 59.7 +/- 6.2 and 60.7 +/- 3.1 mmHg, respectively. These results suggested that the respiratory activity of oocytes seemed to be increased during the early cleavage stage and that this microelectrode technique should be useful in further studies of respiratory metabolism in oocytes and preimplantation embryos.
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O-(alpha-D-Glucopyranosyl)-(1----6)-O-beta-D-glucopyranosyl-(1----6)-1-N -(glycylglycylglycyl-L-seryl-L-leucyl-L-glutam-5-oyl)-alpha- D -glucopyranosylamine has been prepared, as a model of a derivative possibly present in the glomerular basement membrane of rats, by condensation of the corresponding L-glutamyl derivative of the trisaccharide with the pentapeptide in the presence of O,O-diethyl cyanophosphonate. Protective groups were removed by O-deacetylation, deethoxylation, and hydrogenolysis. The glutamyl derivative of the trisaccharide was also converted into the acyl azide which was condensed with bovine serum albumin to form a neoglycoprotein.
The positive inotropic effect of AP-A was studied in anesthetized dogs with a severe stenosis of the left anterior descending coronary artery. Peak positive dP/dt (mm Hg/s) and % segment shortening (%SS) were used as indices of contractile function. AP-A (1.5-5.0 micrograms/kg, i.v.) produced positive inotropic effects globally (dP/dt, 1700 +/- 100 to 2650 +/- 250 mm Hg/s) and locally in the ischemic zone (%SS, 6.7 +/- 1.7 to 13.7 +/- 1.5%) without changing heart rate, mean arterial pressure or myocardial blood flow. These data suggest that AP-A may be potentially useful in the management of heart failure.
In order to elucidate the role of central monoaminergic neurons in electroconvulsive shock (ECS)-induced muricide inhibition in the olfactory bulbectomized rat (OB rat), we examined the effect of chemical or electrical lesions of each monoamine-containing neuron on ECS-induced muricide inhibition. ECS-induced muricide inhibition was antagonized by 6-hydroxydopamine (6-OHDA) treatment and locus coeruleus lesions, while it was unaffected by desipramine + 6-OHDA, substantia nigra lesion, and desipramine + 5,7-dihydroxytryptamine. The present results strongly suggest that ECS-induced muricide inhibition of the OB rat is due to increased activity of the noradrenaline but not of dopamine and serotonin neurons.
In guinea-pig aorta, the potentiating effect of dopamine on the response to arachidonic acid was examined. The potentiation by dopamine was completely abolished by nordihydroguaiaretic acid, but not by indomethacin, aspirin, corticosterone, haloperidol, SK & F 83566, propranolol, PGI2 or imidazole. Dopamine did not have any significant effect on the response to PGF2 alpha U-46619, KCl, 5-hydroxytryptamine or histamine.
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Brevetoxin-B (BTX-B), a Gymnodinium breve toxin, isolated from the dinoflagellate, produced contraction of guinea pig ileum and rabbit aorta. Atropine (10(-6) M) and phentolamine (10(-6) M) abolished the BTX-B (10(-7) or 10(-6)-induced contraction of the ileum or aorta, respectively. Tetrodotoxin and saxitoxin (both 5 x 10(-7) M) also abolished the responses to BTX-B in the both tissues. Results suggest that BTX-B produces smooth muscle contractions through the tetrodotoxin- and saxitoxin-sensitive release of transmitters from autonomic nerves.
The effects of coumarins on anaphylactic mediator release from rat mast cells were investigated. Since Pd-Ia (3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin) causes relaxation of smooth muscle by inhibiting calcium influx, and since mediator release is a calcium-dependent process, studies were made on whether coumarins block calcium influx into rat mast cells stimulated by concanavalin A. Pd-Ia isolated from Peucedanum praeruptorum Dunn and related compounds, named Pd-C-II, Pd-C-III and Pd-C-IV, from Peucedanum decursivum Maxim., (Angelica decursiva Fr. et Sav.) inhibited anaphylactic mediator release from purified mast cells induced by concanavalin A with phosphatidylserine; their IC50 values were 79, 100, 102 and 73 microM, respectively. Pd-III, decursidin and water-soluble analogues of Pd-Ia (Pd-Ia-OH, Pd-Ia-OCH2CH3) did not inhibit the release. Thus the inhibitory actions of coumarins on calcium influx seemed to depend on the chemical structures of these compounds; an acetoxyl residue at position 3' or 4' on the seselin or xanthyletin skeleton might be essential for an inhibitory effect. Furthermore, Pd-Ia and Pd-C-III caused more than 40% reduction in 45Ca uptake induced by concanavalin A, whereas decursidin had little effect on it. Therefore, the inhibitions of mediator release of mast cells by some of coumarins from "Qian-Hu" seem to depend on their effects in blocking calcium influx.
Behavioral effects of amantadine, especially on abnormal behavior in mice and rats, were reevaluated, in comparison with those of tricyclic antidepressants, methamphetamine and L-DOPA. 1) Amantadine at 10 approximately 50 mg/kg, i.p., tended to decrease ambulation and rearing in rats and mice. The drug at 50 mg/kg, i.p., caused piloerection and hyperirritability and at doses over 80 mg/kg, i.p., it impaired coordinated motor activity in rats. 2) Amantadine inhibited methamphetamine-induced hyperactivity, but apomorphine-induced stereotyped behavior was unaffected in rats. 3) Amantadine was equipotent to imipramine in suppressing haloperidol-induced catalepsy in rats, but L-DOPA was without effect. On the other hand, amantadine was 40 and 400 times as potent as imipramine and L-DOPA, respectively, in suppressing delta 9-tetrahydrocannabinol (THC)-induced catalepsy in rats. 4) Amantadine was as potent as imipramine in suppressing the muricide of olfactory bulbectomized rats, but was 3.5, 8.8 and 225.5 times as potent as methamphetamine, imipramine and L-DOPA, respectively, in inhibiting THC-induced reversible muricide in rats. 5) Amantadine at 50 mg/kg did not elicit circling behavior in the rat with unilateral nigral lesion induced by 6-hydroxydopamine. 6) Amantadine at high doses caused irritable aggression characterized by squealing in rats pretreated with intraventricular 6-hydroxydopamine. The most important characteristic of amantadine is its prominent effect suppressing the THC-induced catalepsy and muricide. This may be a reflection of the feature of amantadine activating the dopaminergic as well as the serotonergic systems.
Behavioral and electroencephalographic effects of lormetazepam were investigated in rats, mice and rabbits, in comparison with those of diazepam, nitrazepam and flurazepam. Locomotor activity of mice in an open-field situation was decreased with large doses of lormetazepam and diazepam, while it was increased with nitrazepam and flurazepam. The anticonflict effect of lormetazepam in rats was much more potent than those of diazepam, nitrazepam and flurazepam. In suppressing the muricide of olfactory bulbectomized and raphe lesioned rats, lormetazepam was more potent than diazepam, nitrazepam and flurazepam. Lormetazepam, diazepam and flurazepam prevented both maximal electroshock and pentetrazol convulsions in mice, the effects on the latter being much more potent than those on the former. Lormetazepam was more potent than diazepam and flurazepam in potentiating thiopental-, ether- and ethanol anesthesia, impairing rotarod performance and in muscle relaxant activity. In conscious rabbits with chronically implanted electrodes, lormetazepam induced a drowsy EEG pattern and suppressed the EEG arousal responses not only to auditory stimulation but also to electrical stimulation of the midbrain reticular formation or hypothalamus. Lormetazepam also inhibited afterdischarges induced by electrical stimulation of the hippocampus and amygdala. These results indicate that lormetazepam has pharmacological properties characteristic of benzodiazepines and that the activity is more potent than those of diazepam, nitrazepam and flurazepam.
The effects of electroconvulsive shock (ECS) on the hyperemotionality and muricide in olfactory bulbectomized rats (OB rat) were compared with those in spontaneous killer rats (SP rat), raphe lesioned rats (Raphe rat) and delta 9-tetrahydrocannabinol treated rats (THC rat). Single and chronic treatment of ECS inhibited the muricide and attack response to a rod, but did not affect the struggle response to handling and flight response to air blowing. Muricide was markedly inhibited by ECS in OB and SP rats, and was moderately inhibited in THC rats, while it was slightly inhibited in Raphe rats. The present result indicates that muricide of OB rats is a useful model for evaluating antidepressant drugs as this behavior is markedly inhibited by ECS in OB rats. Furthermore, it is suggested that the effect of ECS on muricide is different depending upon the methods to induce muricide, although muricide itself seems to be behaviorally similar.
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