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Biomedical subjects

T Tatsuno

Publications and source records attributed to T Tatsuno.

At least 37 records · Page 2Linked to original sources
PubMed1993

Basic FGF, NGF, and IGFs protect hippocampal and cortical neurons against iron-induced degeneration.

Iron is believed to contribute to the process of cell damage and death resulting from ischemic and traumatic insults by catalyzing the oxidation of protein and lipids. Exposure of cultured rat hippocampal neurons to iron (FeSO4) caused a dose-dependent reduction in neuronal survival, which was potentiated by ascorbate. Damage to neurons was associated with a significant level of oxygen radical in the culture medium. The iron chelator desferal prevented both the neuronal degeneration caused by FeSO4 and the production of oxygen radical, demonstrating that ionic iron was responsible for the cell damage. Iron neurotoxicity was associated with an elevation of [Ca2+]i and was attenuated by NMDA receptor antagonists. Since recent findings demonstrated neuroprotective effects of growth factors in cell culture and in vivo models of ischemia, we examined the effects of growth factors on iron-induced damage. Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and insulin-like growth factors (IGF-I and IGF-II) each protected neurons against iron-induced damage. Both rat hippocampal and human cortical neurons were protected by these growth factors. Taken together, the data suggest that the neuroprotective effects of growth factors against excitotoxic/ischemic insults may result, in part, from a prevention or attenuation of oxidative damage.

Animals↗
PubMed1993

Effects of SM-9018, a potential atypical neuroleptic, on the central monoaminergic system in rats.

The effects of SM-9018, a potential atypical neuroleptic, on monoamine metabolism were studied in rats. SM-9018 dose-dependently increased the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the cerebral cortex and striatum without affecting the levels of 5-HT, norepinephrine and their metabolites. This action persisted for 8 hr with a maximum effect at 1-2 hr. The SM-9018-induced increase of dopamine (DA) turnover, as indexed by HVA/DA and DOPAC/DA ratios, was comparable in the cerebral cortex and striatum, whereas the typical neuroleptic haloperidol preferentially enhanced the striatal DA turnover. These findings suggest that SM-9018, unlike haloperidol, increases DA turnover to a similar extent both in the cerebral cortex and striatum.

Animals↗
PubMed1992

Serotonergic mechanisms in anxiolytic effect of tandospirone in the Vogel conflict test.

To clarify which 5-HT1A receptors, autoreceptors located in the raphe nuclei or post-synaptic receptors in the forebrain areas receiving a 5-HT input, mediate the anticonflict action of tandospirone (a 5-HT1A receptor-related anxiolytics), the behavioral effects of tandospirone were studied in 5,7-dihydroxytryptamine (5,7-DHT) treated rats. By measuring both monoamines and their metabolite levels and densities of [3H]8-OH-DPAT binding in 5,7-DHT-treated rat brain, we confirmed that pretreatment with 5,7-DHT destroyed 5-HT neurons selectively without affecting postsynaptic 5-HT1A receptors located on the postsynaptic neurons. This selective destruction produced no significant changes in the drinking behavior of rats in either punished or unpunished sessions of the Vogel conflict test. Furthermore, this destruction altered neither the effect of tandospirone on punished responding in this procedure nor the potency of tandospirone to induce a flat body posture in rats, which is known as the "serotonin behavioral syndrome". These results suggested that the anticonflict action of tandospirone may be produced, at least in part, by binding to postsynaptic 5-HT1A receptors and activating them as agonists, and not to 5-HT1A autoreceptors located on the cell bodies of 5-HT neurons.

5,7-Dihydroxytryptamine↗
PubMed1991

Autoradiographic localization and pharmacological characterization of [3H]tandospirone binding sites in the rat brain.

The regional distribution and pharmacological properties of [3H]tandospirone binding sites in the rat brain were investigated using quantitative autoradiography. [3H]Tandospirone binding was notably high in the dentate gyrus and CA1 area of the hippocampus, lateral septum, entorhinal cortex, interpeduncular nucleus and dorsal raphe nucleus. The distribution profiles of [3H]tandospirone binding sites significantly correlated with that of serotonin (5-HT)1A receptors identified using [3H]8-OH-DPAT. In competitive binding studies, [3H]tandospirone binding was inhibited by 5-HT, 8-OH-DPAT, pindolol, buspirone and N-(a,a,a-trifluoro-m-tolyl)-piperazine. The potencies of these ligands correlated with their affinities for 5-HT1A receptors. In addition, there was no significant difference in the dissociation constant of [3H]tandospirone binding between the dentate gyrus, CA1 area, dorsal raphe nucleus, lateral septum and entorhinal cortex (about 10 nM) suggesting that [3H]tandospirone binds to 5-HT1A receptors with same affinities in these brain structures. The distribution pattern of binding sites for [3H]tandospirone was also compared with that of benzodiazepine receptors identified using [3H]fludiazepam to find common effector sites for different types of anxiolytics. Some similarities were observed. It is evident in the hippocampal formation that an overlap of intense binding occurred. 5-HT1A receptors in the hippocampus may participate in the anxiolytic effects of tandospirone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Autoradiographic evidence for the interaction of SM-3997 with 5-HT1A receptors in the rat brain.

[3H]8-OH-DPAT binding to rat brain sections and inhibition by SM-3997 were investigated. Very high densities of [3H]8-OH-DPAT binding sites were found in the dentate gyrus, entorhinal cortex, dorsal raphe, interpeduncular nucleus and lateral septum. In contrast, their densities were sparse in the substantia nigra, caudate putamen and choroid plexus. In the presence of 1 microM of SM-3997, [3H]8-OH-DPAT binding was strongly inhibited in all the brain structures we examined. These results indicate that SM-3997 binds to 5-HT1A receptors of rat brain sections.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

[The condition of dentition and the prediction of eruption at lower third molars of Japanese adolescent males].

This study was examined the relationships between the condition of dentition of lower third molar and malocclusions and shape of mandibles, and to predict eruption for third molars by their relationships. Data were obtained from 90 degrees and 60 degrees rotated cephalometlic radiographs, orthopantomographic radiographs, mandibular occlusal films and gnathostatic models of 101 males showing a complete permanent dentition anterior to the second molars and who had not had extraction lower their molars and orthodontic treatments, were selected from 147 dental students at Asahi University. they were divided into 8 groups by condition of lower third molar dentitions. Bilateral presence of lower third molar occurred in 69.3% and unilateral in 20.8% on 60 degrees rotated cephalometlic radiographs. Bilateral eruption or half eruption occurred in 24.7% and impaction in 44.6% on gnathostatic models. Coronal arch length of erupted cases was longer than that of impacted cases. A apired t-test revealed the significant difference (p less than 0.05). Over bite of impacted cases were deeper than that of erupted cases (p less than 0.05). Arch length discrepancy of presented and impacted cases were larger. There were normal occlusions in each group. Most mal-occlusions were prognathia, second to deep bite, bi-maxillary. The most frequent lower arch conditions were crowding (65%). I. M. P. A. of bilateral impacted cases were langer. Mandiblar length (Cd-Pog) of erupted cases were longer. The distance from Xi-point to the distal surface of second molar was border at 25mm for lower third molar eruption.

Adolescent↗
PubMed1989

Effects of the putative anxiolytic SM-3997 on central monoaminergic systems.

The effects of SM-3997 on central monoaminergic systems were evaluated by ex vivo measurement of monoamines and their metabolite levels in rat brain after intraperitoneal treatment of drugs and by in vitro measurement of monoamine uptake into rat brain slices. The effects of SM-3997 were also compared with those of other new nonbenzodiazepine anxiolytic compounds. SM-3997, buspirone, gepirone and ipsapirone showed no effects on serotonin uptake and dopamine uptake, and a weak inhibition of norepinephrine uptake at the concentration of 100 microM. SM-3997 decreased the serotonin metabolite (5-hydroxyindole-3-acetic acid) level without changing the serotonin level in hippocampus and increased dopamine metabolite (3,4-dihydroxyphenylacetic acid, homovanillic acid) level with no effect on the dopamine level in striatum. SM-3997 also produced an increase in the norepinephrine metabolite (3-methoxy-4-hydroxyphenylglycol) level with a decrease in the norepinephrine levels in hippocampus. Similar effects on serotonin metabolites and norepinephrine metabolites were observed in several other regions. Although the serotonergic effect of SM-3997 was similar to that of buspirone, gepirone and ipsapirone, the dopaminergic effect of SM-3997 was much weaker than that of buspirone.

Animals↗
PubMed1988

Characterization of the putative anxiolytic SM-3997 recognition sites in rat brain.

In order to clarify the mechanism of action of the putative nonbenzodiazepine anxiolytic SM-3997 [3a alpha,4 beta,7 beta,7a alpha)-Hexahydro-2-(4-(4-(2-pyrimidinyl)-1- piperazinyl)-butyl)-4,7-methano-1H-isoindole-1,3 (2H)-dione dihydrogen citrate), in vitro binding studies with radiolabeled compound were performed. 3H-SM-3997 bound rapidly, reversibly and in a saturable manner with high affinity to rat brain hippocampal membranes (Kd = 9.4 nM, Bmax = 213 fmol/mg protein). This specific binding was displaced by 5-hydroxytryptamine (5-HT) and related compounds. Especially, 8-OH-DPAT, a 5-HT-1A selective agonist, bound with the highest affinity to these binding sites. 3H-SM-3997 binding, however, was not displaced by a variety of other neurotransmitters, neuropeptides and some other drugs. EDTA and physiological concentration of Na+ inhibited this specific binding, but several divalent cations, Mn2+, Ca2+ and Mg2+, enhanced this binding. GTP decreased the affinity of these binding sites for 3H-SM-3997 without changing the number of binding sites, but GMP and ATP did not influence 3H-SM-3997 binding. Furthermore, 3H-SM-3997 bound with marked regional selectivity to hippocampal membranes. These characteristics and the regional distribution of 3H-SM-3997 binding sites were very similar to those of 3H-8-OH-DPAT binding sites (5-HT-1A receptors). Therefore, these results indicate that SM-3997 binds selectively and with high affinity to 5-HT-1A receptors in rat brain and may be an agonist.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Inhibition by forskolin of excitatory amino acid-induced accumulation of cyclic AMP in guinea pig hippocampal slices.

The effect of forskolin on the excitatory amino acid-induced accumulation of cyclic AMP was examined in hippocampal preparations of the guinea pig. Forskolin at concentrations of 0.1-10 microM remarkably enhanced the stimulatory effects of histamine and adenosine, whereas it markedly attenuated the stimulation induced by cysteine sulfinate, an excitatory amino acid. Forskolin reduced the maximal response to cysteine sulfinate without affecting the apparent ED50. At a concentration of 1 microM, forskolin also inhibited the stimulatory effects of glutamate, N-methyl-DL-aspartate, and veratridine without affecting those of kainate and quisqualate. Pretreatment of the slices with 0.1 mM N-ethylmaleimide partially prevented the attenuation by forskolin of cysteine sulfinate-induced accumulation of cyclic AMP without affecting the stimulation induced by cysteine sulfinate. Forskolin at concentrations of less than 1 microM did not affect GTP-stimulated activity and Cl- -dependent activity of adenylate cyclase of the hippocampal membranes.

Adenosine↗
PubMed1988

Interaction of SM-3997 with serotonin receptors in rat brain.

The propensity of SM-3997 to displace 3H-ligands was tested in vitro in a number of receptor-binding assays. SM-3997 possessed a high affinity towards 5-HT1A receptors, low affinity towards dopamine (D2) and 5-HT2 receptors, and no affinity towards benzodiazepine (BZ), GABA, 5-HT1B and adrenergic receptors. Moreover, SM-3997 facilitated neither 3H-flunitrazepam binding nor 3H-muscimol binding. These results suggest that the action of SM-3997 may be mediated via central 5-HT1A receptors but not the BZ-GABA receptor complex.

Animals↗
PubMed1987

Pharmacological properties of SM-3997: a new anxioselective anxiolytic candidate.

Pharmacological properties of SM-3997 (3a alpha,4 beta,7 beta,7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1- piperazinyl)-butyl)-4,7-methano-1H-isoindole-1,3(2H)-dione dihydrogen citrate) have been examined in rats and mice. SM-3997 showed a dose-related anticonflict activity in rats in a water lick conflict paradigm, and it had no effect on water consumption in a spontaneous water drinking test. The potency of SM-3997 appeared to be equal to that of buspirone and about one-half that of diazepam. No tolerance to the anticonflict activity of SM-3997 was observed following 5 and 10 consecutive days of treatment. Unlike diazepam, SM-3997 had no anticonvulsant effect and had very weak muscle relaxant and hypnotic effects. On the other hand, SM-3997 and buspirone exhibited dopamine antagonistic action, although the potency of SM-3997 was less than one fourth that of buspirone. These results show that SM-3997 is a new anxioselective anxiolytic agent which is weaker than buspirone in the dopaminergic neuron system.

Anesthesia↗
PubMed1985

Membrane-bound lipoxygenase of rat cerebral microvessels.

The microvessels isolated from rat cerebral cortex has arachidonate lipoxygenase activity, which was not due to possible contamination of the platelets. The major product was identified to be 12-hydroxyeicosatetraenoic acid. After homogenization and sonication of the microvessel preparations, the lipoxygenase activity was recovered both in the membrane- and the cytosol-fractions, whereas that in the platelets was recovered in the cytosol fraction. Membrane-bound lipoxygenase of the microvessels has apparent Km value of 3.8 microM for arachidonic acid, which was corresponded to 1/5 of that in the platelet enzyme. Microvessel lipoxygenase was inhibited by nordihydroguaiaretic acid but not by indomethacin.

Animals↗
PubMed1985

Trichothecene structure and toxicity to the green alga Chlorella pyrenoidosa.

Using the paper-disk method with Chlorella-seeded agar plates, 15-acetoxyscirpenol, HT-2 toxin, acetyl T-2 toxin and neosolaniol inhibited growth at a concentration of 1 mg/ml, whereas verrucarol, T-2 tetraol, nivalenol, fusarenon-X, deoxynivalenol and 3-acetyldeoxynivalenol were inactive. Taking into account that verrucarin A, roridin A, T-2 toxin and diacetoxyscirpenol had previously been found to strongly inhibit Chlorella growth, esterification at R15 appears to be important for growth inhibitory activity. The most active agents are also esterified at R4. Inhibition of protein synthesis appears to be involved in the toxicity.

Chlorella↗