Biomedical subjects

Yumi Sugimoto

Publications and source records attributed to Yumi Sugimoto.

At least 19 recordsLinked to original sources

PubMed2006

Strain differences of neurosteroid levels in mouse brain.

Neurosteroids, pregnenolone (Preg), dehydroepiandrosterone (DHEA) and their sulfates (PregS and DHEAS) are reported to exert their modulatory effects of neuronal excitability and synaptic plasticity via amino acid receptors, which affect and regulate the learning and memory process, mood, and depression. Although the brain levels of these steroids have been reported in rodents, the strain differences of the levels of these steroids have not been demonstrated. We examined the concentrations of Preg, 17-OH-Preg, DHEA, androstenediol (ADIOL) and their sulfates in whole brains from DBA/2, C57BL/6, BALB/c, ddY and ICR mice, the genetic backgrounds of which are different. No differences in the brain levels of Preg and DHEA were found among the strains. In contrast, PregS levels in DBA/2 were significantly lower than in the others, while DHEAS concentrations in DBA/2 were significantly higher than those in other strains. Strain differences were found in 17-OH-Preg, ADIOL and 17-OH-PregS but not in ADIOLS levels. The ranges of Preg and PregS levels were the highest among the steroids studied. Further, we measured serum these steroid levels. Although strain differences were also found in serum steroids, correlation study between brain and serum levels revealed that brain neurosteroids studied may not come from peripheral circulation. In conclusion, this is the first report of demonstrating mammalian brain levels of 17-OH-Preg, ADIOL, 17-OH-PregS and ADIOLS and the strain differences in neurosteroid levels in mice brains. The differences in levels may involve the strain differences in their behavior, e.g. aggression, adaptation to stress or learning, in mice.

Animals↗

PubMed2006

Different effects of optical isomers of the 5-HT1A receptor antagonist pyrapyridolol against postischemic guinea-pig myocardial dysfunction and apoptosis through the mitochondrial permeability transition pore.

The recovery (%) of the left ventricular developed pressure by (S)-(-)-pyrapyridolol (5 x 10(-8) M) (90.7%), an optical isomer of a new 5-HT1A receptor antagonist, was greater than that by (R)-(+)-pyrapyridolol (66.2%, control: 34.4%) against ischemia-reperfusion injury in perfused Langendorff guinea-pig hearts. In the perfused mitochondrial preparation, (S)-(-)-pyrapyridolol inhibited the mitochondrial Ca2+ (Cam) elevation that was brought about by the change of Ca2+ content or pH of perfusate, similar to findings with cyclosporin A, well known to be an inhibitor of the mitochondrial permeability transition pore (MPTP). The mitochondrial K(ATP) channel opener, diazoxide, also inhibited the Cam elevation, but the mitochondrial K(ATP) channel antagonist, 5-hydroxydecanoic acid, attenuated it. There were significantly fewer numbers of TUNEL-positive cells in these (S)-(-)-pyrapyridolol-treated hearts than the control or (R)-(+)-pyrapyridolol, with decreases of the caspase-3 activity. Therefore, these results suggest that (S)-(-)-pyrapyridolol likely inhibits the opening of the MPTP by preventing the Cam overload induced apoptosis related to endogenous 5-HT accumulation in ischemia-reperfusion hearts.

Adenosine Triphosphate↗

PubMed2006

Involvement of leptin in hypophagia induced by the serotonin precursor 5-hydroxytryptophan (5-HTP) in mice.

We previously demonstrated that a serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) increases serum leptin levels in mice. It was reported that administration of 5-HTP elicits hypophagia in rodents and humans. In the present study, we examined involvement of leptin in 5-HTP-elicited decreases in the milk intake of fasted mice. Serum leptin levels increased with increases in milk intake in mice, while 5-HTP strongly decreased milk intake in fasted mice compared to that in the control group. Serum leptin levels in fasted mice treated with 5-HTP were similar to those control mice after milk intake. As leptin is a powerful anorectic signal, 5-HTP-induced anorexia may be mediated by facilitation of leptin secretion.

5-Hydroxytryptophan↗

PubMed2005

Protective effects of sarpogrelate, a 5-HT2A antagonist, against postischemic myocardial dysfunction in guinea-pig hearts.

The protective effects of sarpogrelate (SG), a 5-HT2A antagonist, were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. Changes in cellular levels of high phosphorous energy, NO and Ca2+ in the heart together with simultaneous recordings of left ventricular developed pressure (LVDP) were monitored using an nitric oxide (NO) electrode, fluorometry and 31P-NMR. The recovery of LVDP from ischemia by reperfusion was 30.1% in the control, while the treatment with SG (5 x 10(-7) M) in pre- and post-ischemia hearts produced a gradual increase to 73.1 and 53.6%, respectively. At the final stage of ischemia, the intracellular concentration of Ca2+ ([Ca2+]i) and release of NO increased with no twitching and remained at a high steady level. The addition of SG increased the transient NO signal (TNO) level at the end of ischemia compared with the control, but [Ca2+]i during ischemia decreased. Meanwhile, mitochondrial Ca2+ uptake on acidification or Ca2+ content changes of the perfusate was suppressed by pre-treatment with SG or the KATP channel opener diazoxide, but not the KATP channel blocker 5-HD. The myocardial NO elevated with 5-HT in normal Langendorff hearts was suppressed by the treatment with SG. Therefore, the existence of the 5HT2A receptor in a Langendorff heart was anticipated. By in vitro EPR, SG was found to directly quench the hydroxy radical. Thus, these findings suggested that the 5-HT2A receptor induced in ischemia-reperfusion plays an important role in the mitochondrial KATP channel of hearts in close relation with NO and active oxygen radicals.

Animals↗

PubMed2005

Relationship between brain serotonin transporter binding, plasma concentration and behavioural effect of selective serotonin reuptake inhibitors.

1. The present study was undertaken to characterise the relationship between in vivo brain serotonin transporter (SERT) binding, plasma concentration and pharmacological effect of selective serotonin reuptake inhibitors (SSRIs) in mice. Oral administration of fluvoxamine, fluoxetine, paroxetine and sertraline at pharmacologically relevant doses exerted dose- and time-dependent binding activity of brain SERT as revealed by significant increases in KD for specific [3H]paroxetine binding, and the in vivo SERT-binding potency was in the order of paroxetine>>fluoxetine, sertraline>fluvoxamine. 2. The time courses of brain SERT binding by SSRIs in mice were mostly in parallel to those of their plasma concentrations. Also, norfluoxetine (active metabolite) has been suggested to contribute largely to the long-lasting binding activity of brain SERT after the fluoxetine administration. 3. Oral administration of each SSRI suppressed significantly the marble-burying behaviour with no change in locomotor activity in mice, and the extent and time course of suppression agreed well with those of brain SERT binding. Thus, the pharmacological potencies of SSRIs in the attenuation of marble-burying behaviour correlated significantly with their brain SERT binding activities. 4. In conclusion, the present study has provided the first in vivo evidences to support that fluvoxamine, fluoxetine, paroxetine and sertraline orally administered bind to the pharmacologically relevant brain SERT in mice and that their SERT-binding characteristics is closely associated with the pharmacokinetics and inhibition of marble-burying behaviour.

Animals↗

PubMed2005

Inhibitory effects of the 5-HT(1A) receptor agonist buspirone on stress-induced hyperglycemia in mice: involvement of insulin and a buspirone metabolite, 1-(2-pyrimidinyl)piperazine (1-PP).

Effects of serotonergic anxiolytic buspirone on immobilization-induced hyperglycemia were studied in mice. Stress elicited hyperglycemia in mice. Pretreatment with buspirone significantly reduced immobilization-induced hyperglycemia. Buspirone increased serum insulin levels in both non- and stressed mice. The major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP) also increased and this further inhibited immobilization-induced hyperglycemia, since 1-PP increased serum insulin levels in both non-stressed and stressed mice, similar to the increases induced by buspirone. These results suggest that buspirone can reduce stress-induced hyperglycemia by facilitating insulin release. Moreover, 1-PP, a metabolite of buspirone may participate in the effects of buspirone. Since 1-PP is an antagonist of alpha(2) receptors, alpha(2) receptors may be related to effects of 1-PP.

Animals↗

PubMed2005

[Questionnaire survey about an anesthesia information sheet].

BACKGROUND: The anesthesia information sheet used in our hospital describes the anesthetic management and complications in a simple style. Patients scheduled for operations receive it from their doctor with some explanation about anesthesia. The written informed consent on the sheet is obtained from the patients. METHODS: One hundred and one patients undergoing elective operations were interviewed after receiving explanations during the anesthesiologist's preoperative rounds. RESULTS: From this survey, 85% of the patients read it before the anesthesiologist's preoperative rounds and 75% of them understood the contents. After the anesthesiologist's explanation, 94% of the patients who had read it understood enough. About a third of the patients who had read the information sheet had anxiety about anesthesia. After the anesthesiologist's explanation, the percentage of patients who had anxiety decreased to 8%. 98% of the patients who read the information sheet answered that it should be read before the anesthesiologist's preoperative rounds. CONCLUSIONS: In view of this survey we concluded that reading the information sheet before the anesthesiologist's preoperative rounds is useful to increase the patients understanding of anesthesia.

Anesthesia↗

PubMed2004

Involvement of dopamine receptors in the anti-immobility effects of dopamine re-uptake inhibitors in the forced swimming test.

The effects of dopamine re-uptake inhibitors, bupropion and nomifensine on immobility in the forced swimming test were studied in mice. Bupropion and nomifensine reduced immobility time dose-dependently. Both drugs significantly displayed anti-immobility effects at doses without altering locomotor activity. Anti-immobility effects of bupropion and nomifensine were inhibited by the dopamine D1 receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-HCl (SCH 23390) and the dopamine D2 receptor antagonist sulpiride. These findings suggest that dopamine may be related to depression and dopamine D1 and dopamine D2 receptors play a role in the effects of dopamine re-uptake inhibitors.

Animals↗

PubMed2004

Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in mice.

The pharmacological effects of extracts of Hypericum perforatum (St John's wort) were characterized in-vitro and ex-vivo, in relation to its behavioural effects. In in-vitro experiments, St John's wort inhibited brain synaptosomal [(3)H]serotonin uptake in mice with little effect on specific [(3)H]paroxetine binding. For selective serotonin-reuptake inhibitors (SSRIs), the IC50 value for [(3)H]serotonin uptake (molar concentration of unlabelled drug necessary to displace 50% of specific uptake) correlated well with the inhibition constant K(i) value for [(3)H]paroxetine binding in mouse brain. Oral administration of St John's wort (900 mg kg(-1)), paroxetine (1 mg kg(-1)) and sertraline (10 mg kg(-1)) brought about significant increases in the K(m) value for [(3)H]serotonin uptake into brain synaptosomes 4 h later, and only SSRIs suppressed specific [(3)H]paroxetine binding in mouse brain. St John's wort and SSRIs significantly inhibited marble-burying behaviour in mice and the time-course of attenuation of this behaviour by St John's wort was similar to that of [(3)H]serotonin uptake inhibition. In the forced swimming test, St John's wort, but not SSRIs, suppressed the immobility time of mice after oral administration. These results provide the first in-vivo evidence to suggest that the mode of antidepressant action of St John's wort differs from that of SSRIs. Thus, this study may have a significant impact on phytotherapy with St John's wort.

Administration, Oral↗

PubMed2003

Hyperleptinemia elicited by the 5-HT precursor, 5-hydroxytryptophan in mice: involvement of insulin.

Mechanisms for hyperleptinemia elicited by a serotonin (5-hydroxytryptamine, 5-HT) precursor, 5-hydroxytryptophan (5-HTP), were investigated. 5-HTP elicited apparent increases in serum leptin levels of mice. Administration of 5-HTP did not alter expression of leptin mRNA in white adipose tissues. Furthermore, neither 5-HTP nor 5-HT increased leptin secretion from isolated fat pads of mice. Since insulin is known to enhance leptin release, involvement of insulin in 5-HTP-induced hyperleptinemia was examined. 5-HTP significantly elevated serum insulin levels. In mice treated with streptozotocin, which depletes insulin, 5-HTP did not increase serum leptin levels. These results suggest that hyperinsulinemia participates the elevation of serum leptin levels elicited by 5-HTP.

5-Hydroxytryptophan↗

PubMed2003

Role of serotonergic mechanisms in leptin-induced suppression of milk intake in mice.

Effects of leptin on milk consumption in food-deprived mice were investigated. In this feeding model, systemic administration of leptin reduced milk intake of mice dose-dependently. Decreases in milk intake elicited by leptin were significantly reduced by the serotonin (5-HT) synthesis inhibitor p-chlorophenylalanine (PCPA). The suppressive effects of leptin on milk intake were antagonized by the 5-HT(2B/2C) receptor antagonist SB206553, while the 5-HT(1B) receptor antagonist GR55562 and the 5-HT(2A) receptor antagonist ketanserin did not affect it. Our results indicated that the 5-HT depleter PCPA and the 5-HT(2B/2C) receptor antagonist SB206553 attenuated leptin-induced suppression of milk intake. Therefore, leptin-induced hypophagic effects may be mediated by enhancement of serotonergic neurons, resulting in activation of the 5-HT(2B/2C) receptor.

Animals↗

PubMed2003

Leptin inhibits food intake without affecting brain NOx levels in food-deprived mice.

Effects of leptin on food intake and nitric oxide (NO) metabolites (nitrite and nitrate, NOx) levels of brain were investigated in mice. Leptin dose-dependently decreased milk intake in food-deprived mice. Administration of leptin at a dose of 1 mg/kg, which induces an apparent hypophagia, did not affect NOx levels in the hypothalamus and frontal cortex. These results suggest that leptin reduces food intake in food-deprived mice without altering NO production in the hypothalamus, which plays an important role in regulation of feeding.

Animals↗

PubMed2003

Effects of insulin and adrenalectomy on elevation of serum leptin levels induced by 5-hydroxytryptophan in mice.

We previously reported that a serotonin precursor 5-hydroxytryptophan (5-HTP) increases serum leptin levels in mice. In this study, we studied the effects of insulin and adrenalectomy on hyperleptinemia induced by 5-HTP. Co-administration of insulin significantly increased hyperleptinemia elicited by 5-HTP. 5-HTP itself increased serum insulin levels. Adrenalectomy, which depletes corticosterone, did not abolish hyperleptinemic effects of 5-HTP. These results suggest that insulin may participate in hyperleptinemic effects of 5-HTP and that the involvement of corticosterone in effects of 5-HTP may be probably small.

5-Hydroxytryptophan↗

PubMed2003

Effects of the serotonergic anxiolytic buspirone on plasma glucose and glucose-induced hyperglycemia in mice.

Effects of the serotonergic anxiolytic buspirone on plasma glucose and glucose-induced hyperglycemia were studied in mice. Buspirone did not affect plasma glucose levels of non-fasted mice, while it increased serum insulin levels. In fasted mice, buspirone significantly reduced glucose-induced hyperglycemia and enhanced insulin release elicited by glucose. This suggests that buspirone enhances insulin release, resulting in inhibition of glucose-induced hyperglycemia. The major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP) increased serum insulin levels and induced a slight hypoglycemia in non-fasted mice. 1-PP decreases glucose-induced hyperglycemia and amplifies insulin release elicited by glucose in fasted mice. Since buspirone is mainly metabolized to 1-PP and formation of 1-PP occurs quickly, the inhibitory effect of buspirone on glucose-induced hyperglycemia is likely mediated by 1-PP.

Animals↗

PubMed2003

The tricyclic antidepressant clomipramine increases plasma glucose levels of mice.

Effects of the tricyclic antidepressant clomipramine on plasma glucose levels in mice were studied. Clomipramine at doses ranging 5 - 20 mg/kg elicited significant hyperglycemia in mice. Hyperglycemia elicited by clomipramine was not reduced by pretreatment with the 5-hydroxytryptamine (5-HT) depleter p-chlorophenylalanine. The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it. The 5-HT(2B/2C)-receptor antagonist SB 206553 facilitated hyperglycemia induced by clomipramine, although the 5-HT(2A)-receptor antagonist ketanserin was without effect. Clomipramine-induced hyperglycemia was reduced by prior adrenalectomy. These results suggest that clomipramine induces hyperglycemia in mice by blocking the 5-HT(2B )and/or 5-HT(2C) receptors, which results in facilitation of adrenaline release.

Adrenalectomy↗

PubMed2002

Differential effects of the 5-HT2 receptor antagonist on the anti-immobility effects of noradrenaline and serotonin reuptake inhibitors in the forced swimming test.

The effects of the 5-HT(2) receptor antagonist, LY 53857 on the effects of noradrenaline and serotonin reuptake inhibitors were investigated using the forced swimming test. LY 53857 enhanced anti-immobility effects of clomipramine and maprotiline, which can inhibit reuptake of noradrenaline. However, LY 53857 did not affect the immobility time of mice treated with the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine. These results suggest that antagonism of the 5-HT(2) receptor leads to potentiation of the antidepressant effects of noradrenaline reuptake inhibitors but not SSRIs and that LY 53857 may modify the activity of noradrenergic neurons.

Adrenergic Uptake Inhibitors↗

PubMed2002

Nitric oxide production in hypothalamus of 2-deoxy-D-glucose-treated and food deprived mice.

Nitric oxide (NO) has been suggested to be involved in the regulation of food intake. In the present study, NO metabolite (nitrite and nitrate, NOx) levels in the hypothalamus were determined in hyperphagic mice. In normal mice, NOx levels were higher in the hypothalamus than those in frontal cortex. Although 2-deoxy-D-glucose (2-DG) is known to induce hyperphagia by inhibiting glucose utilization, it did not affect NOx levels in the hypothalamus of mice. NOx concentration in the hypothalamus decreased in 48 h-food deprived mice. In the frontal cortex, neither 2-DG nor food deprivation affected NOx levels. These results suggest that NO production in the hypothalamus does not increase in 2-DG-elicited hyperphagia and that food deprivation reduces hypothalamic NO, probably by inhibiting NO synthase.

Animals↗

PubMed2002

Effects of peripheral administration of 5-hydroxytryptamine (5-HT ) on 2-deoxy-D-glucose-induced hyperphagia in rats.

Effects of peripheral administration of 5-HT (5-hydroxytryptamine, serotonin) on hyperphagia induced by 2-deoxy-D-glucose(2-DG) were studied in rats. It was found that 5-HT i.p. reduced 2-DG-elicited feeding in rats dose-dependently. The 5-HT-induced hypophagia was antagonized by the 5-HT2A receptor antagonist, ketanserin. It is known that 2-DG induces glucoprivation, resulting in hyperphagia and hyperglycemia. However, 5-HT did not affect hyperglycemia induced by 2-DG. These results suggest that peripheral injection of 5-HT reduces 2-DG-induced hyperphagia mediated by the peripheral 5-HT2A receptor and that its effects are not due to enhancement of hyperglycemia.

Animals↗