Yasumi Ogura

Transient increase of cytosolic free calcium in cultured human vascular endothelial cells by platelet-activating factor

The effect of platelet-activating factor (PAF-acether) on cytosolic free calcium, [Ca2+]i, in adherent human vascular endothelial cells in culture was directly determined using a new fluorescent calcium indicator, fura-2. It was found that PAF-acether but not lyso PAF-acether induced a rapid and transient increase in [Ca2+]i in endothelial cells. Restimulation with PAF-acether after the first challenge did not cause further response, while the cells were able to respond to thrombin. In the absence of extracellular calcium, PAF-acether evoked a similar transient increase, suggesting that PAF-acether raises [Ca2+]i mainly by discharging calcium from intracellular pools. PAF-acether-induced rise in [Ca2+]i was completely blocked by a specific antagonist, BN 52021. These results suggest the receptor-mediated increase in [Ca2+]i as an early event in PAF-acether activation of human vascular endothelial cells.

Prostaglandins in Rat Pulp Tissue

Rat pulp tissue contained an appreciable amount of prostaglandins, but sex and age-dependent differences in their concentration were not observed. Pulp tissue released prostaglandins into the incubation medium and indomethacin inhibited the release significantly. Radiochemical studies could not demonstrate the biosynthesis and metabolism of prostaglandins in pulp tissue homogenates.

Characteristics of muricide induced by thiamine deficiency and its suppression by antidepressants or intraventricular serotonin

Abstract Male Wistar rats maintained on a thiamine deficient diet showed muricide aggression. On the 30th day of experimental feeding, the incidence was 70% and the killing latency was very short in the thiamine deficient killer-rats. They did not kill their rat-pups. Intraventricular injection of serotonin (5-HT) was effective in suppressing the muricide induced by thiamine deficiency. The suppressive effect of 5-HT was strongly antagonized by antiserotonergic agents, morphine and chlorpromazine. Moreover, the suppressive effect of 5-HT was potentiated by iproniazid, a monoamine oxidase inhibitor. Various antidepressants had suppressive effects on this muricide to varying degrees. Muricide induced by thiamine deficiency was more potently suppressed by the tricyclic antidepressants which inhibit 5-HT uptake rather than noradrenaline uptake. Our results in these experiments strengthened the hypothesis that central serotonergic neurons are involved in the inhibition of the muricide aggression in thiamine deficient killer-rats.

Receptor-mediated stimulation of aortic prostacyclin release by 5-hydroxytryptamine

5-Hydroxytryptamine (5-HT) stimulated prostacyclin release, measured by radioimmunoassay as 6-keto-prostaglandin F1 alpha, from rat aorta in a dose-dependent manner (3 X 10(-7)-10(-4) M). A statistically significant stimulation was observed at concentrations higher than 3 X 10(-6) M. Norepinephrine also increased prostacyclin release but only at a high concentration (10(-4) M) and histamine (3 X 10(-5) and 10(-4) M) had no significant effect. Among some structurally 5-HT-related analogues, only tryptamine exhibited a dose-dependent stimulatory effect on prostacyclin release but it was slightly less potent than 5-HT. Tryptophan and 5-hydroxytryptophan had no effects whereas 5-hydroxyindoleacetic acid at 10(-4) M stimulated slightly. Prostacyclin release stimulated by 5-HT was depressed by non-specific 5-HT antagonists, methysergide, mianserin and cyproheptadine. In contrast, a specific 5-HT2 antagonist ketanserin (3 X 10(-7)-10(-5) M) had no antagonistic effect. These results suggest that 5-HT stimulates the release of prostacyclin from rat aorta by interaction with receptors distinct from its 5-HT2 subtype.

5-Hydroxytryptamine stimulates the release of prostacyclin but not thromboxane A2 from isolated rat dental pulp

The effect of 5-hydroxytryptamine (5-HT) on the release of prostacyclin and thromboxane (TX) A2 from isolated rat dental pulp was evaluated. 5-HT (1-1,000 microM) caused a dose-dependent and marked stimulation of the release of prostacyclin but not TXA2. Of the 5-HT-related indolealkylamines tested, only tryptamine had a similar stimulatory effect while tryptophan and 5-hydroxytryptophan had no effect. Neither histamine (100 microM) nor bradykinin (100 microM) had such an effect. Our results suggest the possible involvement of 5-HT receptors in 5-HT-induced stimulation of prostacyclin production in rat dental pulp.

Separation of biogenic amines in rat brain on a phosphorylated-cellulose column

Abstract Catecholamines, serotonin, tryptamine, histamine, putrescine, spermidine and spermine were separated on a phosphorylated-cellulose column by stepwise elution with increasing salt concentration and pH. The method was successfully applied to rat brain extract.

Lipid peroxidation modified the effect of phenolic anti-inflammatory drugs on prostaglandin biosynthesis

The effects of phenolic anti-inflammatory drug, MK-447, on prostaglandin (PG) I2 and thromboxane (TX) A2 biosynthesis by rat dental pulp tissue were evaluated in the presence of 10 mM mannitol (MA) or 1 mM ascorbic acid with 0.3 mM Fe2+ (A + F). Although MK-447 alone at 1 and 10 microM had no significant effects, MK-447 at 100 microM stimulated both PGI2 and TXA2 biosynthesis, and suppressed the lipid peroxidation in the pulp tissue as estimated by thiobarbituric acid method. MA also reduced the lipid peroxidation, but had no effect on PG and TX production. However, in the presence of MA, the stimulatory effect of MK-447 was potentiated, and the significant effects were observed at concentrations higher than 1 microM. In contrast, A + F remarkably stimulated the lipid peroxidation, and inhibited both PG and TX biosynthesis. In the presence of A + F, MK-447 showed no stimulatory effect, and contrary, at 100 microM inhibited PG and TX production. These results suggest that the cellular levels of lipid peroxidation exert a significant influence on the effects of phenolic anti-inflammatory drugs like MK-447 on PG biosynthesis. The possible mechanism of action for such drugs has been discussed in view of the significance of lipid peroxidation in inflammatory condition.

Fugu (Puffer-Fish) Poisoning and the Pharmacology of Crystalline Tetrodotoxin in Poisoning

Fugu (puffer-fish) is one of many poisonous fishes. It produces a potent, toxic substance that is found in various of its organs, for example, the ovaries, liver, intestine, skin, and spawn. Although fugu is dangerous to eat, it is very interesting that there are special restaurants for cooking fugu in Japan. Such restaurants are obligated by the Japanese government to prepare the fish in such a way that fugu intoxication will not be a hazard to diners. One will naturally raise the question—what reasons have Japanese for this dangerous custom. This point-blank question is fired at us by many foreigners. Dangerous, but interesting, eating habits have been rooted among Japanese for a long time; in fact, such habits are localized to Japan. However, the white meat of fugu can please the Japanese palate without causing danger, because a very good technique was developed by our ancestors for treating organs contaminated with its toxic substance. This is a rather unique example of food-life history.

Persistent erection in thiamine-deficient rats.

Männliche Wistar‐Ratten, welche mit thiaminfreiem Futter ernährt wurden, zeigten Gewichtsverlust, Abfall der Herzfrequenz, Urinexkretionsstörungen und Symptome einer Polyneuritis. In dieser Studie wird berichtet, daß Dauererektionen bei diesen Ratten vorkommen, daß sich diese Erektionen während des Versuchsablaufes fortsetzten, und daß die Erektionen nach s.c. Injektion von Thiamin‐HCl teilweise schwanden. Eine Ratte in der Thiamin‐Mangelgruppe zeigte schon am 20. Versuchstag eine Dauer‐erektion, wogegen dieser Effekt in dem Kontrollkollektiv nicht beobachtet wurde. Die Erektion war mäßig, der Penis ragte ca. 2 mm vor. Am 25. Tag wurde die Erektion deutlicher, das vorragende Penisstück wurde ca. 5 mm lang. Wichtig ist, daß die einmal ausgebildete Erektion während der gesamten Versuchsdauer kontinuierlich anhielt. Am 30. Tag der Thiamin‐Mangelfütterung zeigten 7 von 11 Ratten Dauererektionen, außerdem neurologische Erscheinungen wie Kreiselbewegungen und Nackensteife. Das Auftreten der Erektionen nahm ständig zu, es betrug am 20. Tag 7%, am 25. Tag 30,7%, am 30. Tag 63,6% und am 33. Tag 100%.

Fluorometric assay of kininase activities in rat tissues.

A simple method for the assay of bradykinin (BK)-degrading enzymes was investigated. The procedure of the method includes enzymatic degradation of BK, separation of the residual BK on a small P-cellulose column (0.6 X 3 cm), and its fluorometrical determination based on the reaction with fluorescamine. BK was separated completely from its fragments produced during enzymatic reaction by the column chromatography. The recovery rate of BK was 96 +/- 3%. Quantitative determinations could be carried out on 0.2 nmol of BK, at least in the fluorometry. This method was available for the assay of the enzymes in tissue homogenates as well as in purified preparations, and its usefulness for the study of the enzymes is presented.