Biomedical subjects

T Onaka

Publications and source records attributed to T Onaka.

At least 19 recordsLinked to original sources

PubMed2007

Effects of the short chain sugar acid 2-buten-4-olide on the hypothalamo-pituitary-adrenal axis in normal and adjuvant-induced arthritic rats.

The effects of intraperitoneal (i.p.) administration of 2-buten-4-olide (2-B4O), an endogenous sugar acid, on the hypothalamo-adenohypophysial system were examined in Lewis rats that were normal and in adjuvant-induced arthritic (AA) rats. In comparison with vehicle-treated rats, the plasma corticosterone and c-fos mRNA levels in the paraventricular nucleus (PVN) of normal rats increased significantly after i.p. administration of 2-B4O. Dual immunostaining revealed that almost all corticotrophin-releasing factor (CRF)-immunopositive neurones in the parvocellular division of the PVN exhibited Fos-like immunoreactivity (LI) 120 min after i.p. administration of 2-B4O (100 mg/kg). In the AA rats, repeated i.p. administration of 2-B4O (100 mg/kg) after immunisation significantly suppressed the expression of clinical symptoms and significantly increased plasma concentrations of corticosterone. Further, repeated i.p. administration of 2-B4O significantly increased CRF mRNA levels in the PVN and pro-opiomelanocortin mRNA levels in the anterior pituitary; however, they did not change arginine vasopressin mRNA levels in the parvocellular division of the PVN. These results suggest that i.p. administration of 2-B4O activates the hypothalamo-pituitary-adrenal (HPA) axis via the activation of CRF neurones in the PVN, and the activation of the HPA axis by i.p. administration of 2-B4O may be associated with the inhibition of AA in rats.

4-Butyrolactone↗

PubMed2006

Prolactin-releasing peptide is a potent mediator of stress responses in the brain through the hypothalamic paraventricular nucleus.

The effects of i.c.v. administration of prolactin-releasing peptide on neurons in the paraventricular nucleus of rats and plasma corticosterone levels were examined by measuring changes in Fos-like immunoreactivity, c-fos mRNA using in situ hybridization histochemistry, and plasma corticosterone using a specific radioimmunoassay. Approximately 80% of corticotropin-releasing hormone immunoreactive cells exhibited Fos-like immunoreactivity in the parvocellular division of the paraventricular nucleus 90 min after i.c.v. administration of prolactin-releasing peptide. The greatest induction of the c-fos mRNA expression in the paraventricular nucleus was observed 30 min after administration of prolactin-releasing peptide, and occurred in a dose-related manner. Plasma corticosterone levels were also significantly increased 30 min after administration of prolactin-releasing peptide. Next, the effects of restraint stress, nociceptive stimulus and acute inflammatory stress on the expression of the prolactin-releasing peptide mRNA in the dorsomedial hypothalamic nucleus, nucleus of the solitary tract and ventrolateral medulla were examined using in situ hybridization histochemistry for prolactin-releasing peptide mRNA. Restraint stress and acute inflammatory stress upregulated the prolactin-releasing peptide mRNA expression in the nucleus of the solitary tract and ventrolateral medulla. Nociceptive stimulus upregulated the prolactin-releasing peptide mRNA expression in the ventrolateral medulla. Finally, we observed that pretreatment (i.c.v. administration) with an anti-prolactin-releasing peptide antibody significantly attenuated nociceptive stimulus-induced c-fos mRNA expression in the paraventricular nucleus. These results suggest that prolactin-releasing peptide is a potent and important mediator of the stress response in the brain through the hypothalamic paraventricular nucleus.

Analysis of Variance↗

PubMed2006

Exaggerated response of arginine vasopressin-enhanced green fluorescent protein fusion gene to salt loading without disturbance of body fluid homeostasis in rats.

We examined the effects of chronic salt loading on the hypothalamic expressions of the enhanced green fluorescent protein (eGFP), arginine vasopressin (AVP) and oxytocin (OXT) genes in AVP-eGFP transgenic rats that expressed eGFP in the hypothalamic AVP-containing neurones. In these rats, salt loading for 5 days caused a marked increase of the eGFP fluorescence in the magnocellular divisions of the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the internal layer of the median eminence. Expression of the eGFP gene was increased seven- to eight-fold in the PVN and SON of salt-loaded rats in comparison with euhydrated rats. By contrast, none of these changes were observed in the suprachiasmatic nucleus. The expression of the AVP and OXT genes was increased 1.5- to two-fold in the PVN and SON of salt-loaded nontransgenic (control) and transgenic rats. There were no differences in the expression levels of the AVP and OXT genes in the PVN and SON between nontransgenic (control) and transgenic animals under normal conditions and after salt loading. In the posterior pituitary gland, the intensity of the eGFP fluorescence did not change after salt loading for 5 days, but increased after 10 days of salt loading. Upon salt loading, significant increases in the plasma AVP concentrations, plasma osmolality and plasma Na+ were observed. Furthermore, there were no significant differences in changes of water intake, food intake, urine volume, urine osmolality, urine Na+ concentrations, and the body weights in both models under normal or salt-loaded conditions. Our results show that the response of the AVP-eGFP fusion gene to chronic salt loading is exaggerated, and humoral responses such as AVP and OXT and the body fluid homeostasis are maintained in AVP-eGFP transgenic rats. The AVP-eGFP transgenic rat gives us a new opportunity to study the dynamics of the AVP system in vivo.

Animals↗

PubMed2005

Cannabinoids modulate synaptic activity in the rat supraoptic nucleus.

In the present study, we investigated the effects of the cannabinoid receptor agonist CP55,940 on excitatory and inhibitory synaptic transmission in the rat supraoptic nucleus. Whole-cell patch clamp recordings were performed on supraoptic neurones in in vitro brain slice preparations. CP55,940 significantly reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents in a concentration-dependent manner. These changes were potently reversed by the CB1 receptor antagonist AM251. The results indicate that cannabinoids modulate the activity of magnocellular neurosecretory neurones by presynaptic inhibition of both excitatory and inhibitory synaptic transmission.

Anesthetics, Local↗

PubMed2004

Neural pathways controlling central and peripheral oxytocin release during stress.

Oxytocin is released from the pituitary gland in response to a variety of stressful stimuli, including noxious stimuli, conditioned fear and exposure to novel environments. These responses are believed to be mediated, at least in part, by noradrenergic projections from the medulla oblongata, and some of these noradrenergic neurones also contain prolactin-releasing peptide (PrRP). Central administration of either PrRP or noradrenaline stimulates oxytocin secretion into the circulation. Stressful stimuli activate PrRP-containing noradrenergic neurones in the medulla oblongata, and it is thus possible that PrRP/noradrenergic projections to the hypothalamus mediate oxytocin responses to stressful stimuli. Here, the roles of brainstem PrRP/noradrenergic projections to the hypothalamus in oxytocin responses to different kinds of stressful stimuli are reviewed, with a particular emphasis on conditioned fear. Roles of dendritic oxytocin release during stress and metabolic factors affecting stress pathways are also discussed.

Animals↗

PubMed2003

Facilitative role of prolactin-releasing peptide neurons in oxytocin cell activation after conditioned-fear stimuli.

Emotional stress activates oxytocin neurons in the hypothalamic supraoptic and paraventricular nuclei and stimulates oxytocin release from the posterior pituitary. Oxytocin neurons in the hypothalamus have synaptic contact with prolactin-releasing peptide (PrRP) neurons. Intracerebroventricular administration of PrRP stimulates oxytocin release from the pituitary. These observations raise the possibility that PrRP neurons play a role in oxytocin response to emotional stress. To test this hypothesis, we first examined expression of Fos protein, an immediate early gene product, in the PrRP neurons in the medulla oblongata after conditioned-fear stimuli. Conditioned-fear stimuli increased the number of PrRP cells expressing Fos protein especially in the dorsomedial medulla. In order to determine whether PrRP cells projecting to the supraoptic nucleus are activated after conditioned-fear stimuli, we injected retrograde tracers into the supraoptic nucleus. Conditioned-fear stimuli induced expression of Fos protein in retrogradely labeled PrRP cells in the dorsomedial medulla. Finally we investigated whether immunoneutralization of endogenous PrRP impairs oxytocin release after emotional stimuli. An i.c.v. injection of a mouse monoclonal anti-PrRP antibody impaired release of oxytocin but not of adrenocorticotrophic hormone or prolactin and did not significantly change freezing behavior in response to conditioned-fear stimuli. From these data, we conclude that PrRP neurons in the dorsomedial medulla that project to the hypothalamus play a facilitative role in oxytocin release after emotional stimuli in rats.

Adrenocorticotropic Hormone↗

PubMed2003

Effects of novelty stress on neuroendocrine activities and running performance in thoroughbred horses.

This study investigated the effects of novelty stress on neuroendocrine activities and running performance in Thoroughbred horses. First, to examine the neuroendocrine responses to novelty stress, we exposed horses to two types of novel environmental stimuli (audiovisual or novel field stimuli). After the stimuli, plasma concentrations of vasopressin, catecholamines and adrenocorticotropin (ACTH), as well as heart rates, were significantly increased in each experiment. Second, we investigated neuroendocrine activities during incremental exercise. Plasma concentrations of vasopressin, catecholamines, ACTH and blood lactate increased as the exercise load increased. Finally, we investigated the effects of novelty stimuli on neuroendocrine activities and running performance during supra-maximal exercise (110% VHRmax). When the novelty stimuli were presented to horses, the increases in plasma vasopressin and catecholamines due to exercise load were significantly smaller than those in the control experiments. Blood lactate during supra-maximal exercise was also significantly lower and total run time until exhaustion was prolonged in the novel environmental stimuli compared to the control. These results suggest that novelty stimuli facilitate vasopressin release from the posterior pituitary in addition to activating the sympatho-adrenomedullary and the hypothalamic-pituitary-adrenocortical axes in thoroughbred horses, and increase exercise capacity, resulting in improvement of running performance during supra-maximal exercise.

Adrenocorticotropic Hormone↗

PubMed2003

Intermittent footshock facilitates dendritic vasopressin release but suppresses vasopressin synthesis within the rat supraoptic nucleus.

Emotional stress inhibits vasopressin release from the pituitary but may facilitate its release from the dendrites in the hypothalamus. We examined effects of intermittently applied footshock upon the amount of vasopressin heteronuclear RNA in the hypothalamus. The footshock decreased plasma vasopressin concentration but increased its extracellular concentration within the supraoptic nucleus. The contents of the vasopressin heteronuclear RNA in the supraoptic nucleus were significantly decreased after the shock. These data suggest that intermittent footshock decreases not only vasopressin release from the axon terminals in the pituitary, but also vasopressin synthesis in the cell bodies in the hypothalamus while the stimulus facilitates vasopressin release from the dendrites in the hypothalamus. The data also suggest differential control of dendritic vasopressin release and synthesis in the hypothalamus.

Animals↗

PubMed2002

Purification and characterization of the monooxygenase catalyzing sulfur-atom specific oxidation of dibenzothiophene and benzothiophene from the thermophilic bacterium Paenibacillus sp. strain A11-2.

A benzothiophene (BT) and dibenzothiophene (DBT) monooxygenase (TdsC), which catalyzes the oxidation of the sulfur atoms in BT and DBT molecules, was purified from Paenibacillus sp. strain A11-2. The molecular mass of the purified enzyme and its subunit were determined to be 200 kDa and 43 kDa by gel filtration and sodium dodecyl sulfate polyacrylamide gel electrophoresis, respectively, indicating a tetrameric structure. The N-terminal amino acid sequence of the purified TdsC completely matched the amino acid sequence deduced from the nucleotide sequence of the tdsC gene reported previously [Ishii et al. (2000) Biophys Biochem Res Commun 270:81-88]. The optimal temperature and pH for the TdsC reaction were 65 degrees C and pH 9, respectively. TdsC required NADH, FMN and TdsD, a NADH-dependent FMN oxidoreductase, for its activity, as was observed for TdsA. FAD, lumiflavin and/or NADPH had some effect on the maintenance of TdsC activity. A comparison of the substrate specificity of TdsC and DszC, the homologous monooxygenase purified from Rhodococcus erythropolis strain KA2-5-1, demonstrated a contrasting pattern towards alkylated DBTs and BTs.

Alkylation↗

PubMed2001

Vasopressin differentially modulates noradrenaline release in the rat supraoptic nucleus.

Vasopressin is released not only from axon terminals in the neurohypophysis but also from soma/dendrite regions in the supraoptic nucleus. In order to investigate presynaptic roles of dendritically released vasopressin, we examined effects of local application of vasopressin upon noradrenaline release within the supraoptic nucleus by a microdialysis method. Noradrenaline release within the supraoptic nucleus was facilitated by local perfusion with high K+ or an NMDA receptor antagonist. Vasopressin augmented noradrenaline increase after high K+ but reduced it after an NMDA receptor antagonist, AP-5. The results suggest that dendritically released vasopressin modulates noradrenaline release within the supraoptic nucleus in a bimodal fashion.

Animals↗

PubMed2001

Responses of magnocellular neurons to osmotic stimulation involves coactivation of excitatory and inhibitory input: an experimental and theoretical analysis.

How does a neuron, challenged by an increase in synaptic input, display a response that is independent of the initial level of activity? Here we show that both oxytocin and vasopressin cells in the supraoptic nucleus of normal rats respond to intravenous infusions of hypertonic saline with gradual, linear increases in discharge rate. In hyponatremic rats, oxytocin and vasopressin cells also responded linearly to intravenous infusions of hypertonic saline but with much lower slopes. The linearity of response was surprising, given both the expected nonlinearity of neuronal behavior and the nonlinearity of the oxytocin secretory response to such infusions. We show that a simple computational model can reproduce these responses well, but only if it is assumed that hypertonic infusions coactivate excitatory and inhibitory synaptic inputs. This hypothesis was tested first by applying the GABA(A) antagonist bicuculline to the dendritic zone of the supraoptic nucleus by microdialysis. During local blockade of GABA inputs, the response of oxytocin cells to hypertonic infusion was greatly enhanced. We then went on to directly measure GABA release in the supraoptic nucleus during hypertonic infusion, confirming the predicted rise. Together, the results suggest that hypertonic infusions lead to coactivation of excitatory and inhibitory inputs and that this coactivation may confer appropriate characteristics on the output behavior of oxytocin cells. The nonlinearity of oxytocin secretion that accompanies the linear increase in oxytocin cell firing rate reflects frequency-facilitation of stimulus-secretion coupling at the neurohypophysis.

Animals↗

PubMed2001

Medullary A1 noradrenergic neurones may mediate oxytocin release after noxious stimuli.

Noxious stimuli facilitate oxytocin release from the pituitary. Oxytocin cells receive excitatory synaptic inputs from the noradrenergic neurones located in the medulla oblongata. Oxytocin release after noxious stimuli is blocked by noradrenaline depletion in the brain. Here, we examined effects of noxious stimuli upon noradrenaline release within the supraoptic nucleus. Electric footshocks or mustard oil application to the foot pad facilitated noradrenaline release in the nucleus. Noradrenaline release after noxious stimuli was impaired by microinjections with a GABA(A) receptor agonist, muscimol, or an alpha 2 adrenoceptor agonist, clonidine, into the A1 noradrenergic cell regions. From these and reported data, we conclude that the medullary A1 noradrenergic neurones contribute, at least in part, to oxytocin release from the pituitary after noxious stimuli.

Adrenergic alpha-Agonists↗

PubMed2001

Trinuclear Zn(II) and Cu(II) homo and heterotrimetallic complexes involving D-glucopyranosyl and biscarboxylate bridging ligands. A substrate binding model of xylose isomerases.

Reactions of MCl(2).nH(2)O with N,N'-bis(D-glucopyranosyl)-1,4,7-triazacyclononane ((D-Glc)(2)-tacn), which was formed from D-glucose and 1,4,7-triazacyclononane (tacn) in situ, afforded a series of mononuclear divalent metal complexes with two beta-D-glucopyranosyl moieties, [M((D-Glc)(2)-tacn)Cl]Cl (M = Zn (11), Cu (12), Ni (13), Co (14)). Complexes 11-14 were characterized by analytical and spectroscopic measurements and X-ray crystallography and were found to have a distorted octahedral M(II) center ligated by the pentacoordinate N-glycoside ligand, (beta-D-glucopyranosyl)(2)-tacn, and a chloride anion. Each D-glucose moiety is tethered to the metal center through the beta-N-glycosidic bond with tacn and additionally coordinated via the C-2 hydroxyl group, resulting in a lambda-gauche five-membered chelate ring. When L-rhamnose (6-deoxy-L-mannose) was used instead of D-glucose, the nickel(II) complex with two beta-L-rhamnopyranosyl moieties, [Ni((D-Man)(2)-tacn)(MeOH)]Cl(2) (15), was obtained and characterized by an X-ray analysis. Reactions of 11 (M = Zn) with [Zn(XDK)(H(2)O)] (21) or [Cu(XDK)(py)(2)] (22) (H(2)XDK = m-xylylenediamine bis(Kemp's triacid imide)) yielded homo and heterotrimetallic complexes formulated as [Zn(2)M'((D-Glc)(2)-tacn)(2)(XDK)]Cl(2) (M' = Zn (31), Cu (32)). The similar reactions of 12 (M = Cu) with complex 21 or 22 afforded [Cu(2)M'((D-Glc)(2)-tacn)(2)(XDK)]Cl(2) (M' = Cu (33), Zn (34)). An X-ray crystallographic study revealed that complexes 31 and 34 have either Zn(II)(3) or Cu(II)Zn(II)Cu(II) trimetallic centers bridged by two carboxylate groups of XDK and two D-glucopyranosyl residues. The M...M' separations are 3.418(3)-3.462(3) A (31) and 3.414(1)-3.460(1) A (34), and the M...M'...M angles are 155.18(8) degrees (31) and 161.56(6) degrees (34). The terminal metal ions are octahedrally coordinated by the (D-Glc)(2)-tacn ligand through three nitrogen atoms of tacn, two oxygen atoms of the C-2 hydroxyl groups of the carbohydrates, and a carboxylate oxygen atom of XDK ligand. The central metal ions sit in a distorted octahedral environment ligated by four oxygen atoms of the carbohydrate residues in the (D-Glc)(2)-tacn ligands and two carboxylate oxygen atoms of XDK. The deprotonated beta-D-glucopyranosyl unit at the C-2 hydroxyl group bridges the terminal and central ions with the C-2 mu-alkoxo group, with the C-1 N-glycosidic amino and the C-3 hydroxyl groups coordinating to each metal center. Complexes 31-34 are the first examples of metal complexes in which D-glucose units act as bridging ligands. These structures could be very useful substrate binding models of xylose or glucose isomerases, which promote D-glucose D-fructose isomerization by using divalent dimetallic centers bridged by a glutamate residue.

Aldose-Ketose Isomerases↗

PubMed2001

Nicotine facilitates noradrenaline release in the rat supraoptic nucleus.

Nicotine injected in the supraoptic nucleus facilitates vasopressin release from the neurohypophysis. Nicotinic acetylcholine receptors have been found not only on vasopressin-producing cell bodies but also on presynaptic nerve terminals in the nucleus. Vasopressin cells receive excitatory synaptic inputs from noradrenergic neurones. To test whether nicotine facilitates noradrenaline release in the supraoptic nucleus, we perfused the supraoptic nucleus with nicotine through a microdialysis probe. Nicotine increased the extracellular noradrenaline concentrations in the nucleus. A noradrenaline uptake inhibitor, desipramine, increased the extracellular noradrenaline concentrations in the nucleus and did not block the noradrenaline increase after nicotine. The results suggest that nicotine acts within the supraoptic nucleus to facilitate noradrenaline release pre-synaptically. This presynaptic action may contribute, in part, to vasopressin release after nicotine.

Anesthesia↗

PubMed2001

Benzo[b]thiophene desulfurization by Gordonia rubropertinctus strain T08.

A benzothiophene-desulfurizing bacterium which has a novel desulfurization pathway was isolated and identified as Gordonia rubropertinctus strain T08. Gas chromatography/mass spectroscopy analysis of the ethyl acetate extract of the culture broth detected benzothiophene sulfoxide, benzothiophene sulfone, benzo[e][1,2]oxathiin S-oxide (BT-sultine), benzo[e][1,2]oxathiin S,S-dioxide (BT-sultone), o-hydroxystyrene, and 2-coumaranone, but not 2-(2'-hydroxyphenyl)ethan-1-al, which has been reported to be a desulfurized product of mesophilic nocardioforms.

Culture Media↗

PubMed2001

Desulfurization of benzothiophene by the Gram-negative bacterium, Sinorhizobium sp. KT55.

Sinorhizobium sp. KT55 was the first Gram-negative isolate to be capable of utilizing benzothiophene as the sole source of sulfur. By GC-MS analysis of metabolites of benzothiophene by this strain, benzothiophene sulfone, benzo[e][1,2]oxathiin S-oxide and o-hydroxystyrene were detected, suggesting that the benzothiophene desulfurization pathway of this strain is benzothiophene-->benzothiophene sulfoxide-->benzothiophene sulfone-->benzo[e][1,2]oxathiin S-oxide-->o-hydroxystyrene. Desulfurization activity of this strain was significantly repressed by methionine, cysteine, sulfate, dimethyl sulfoxide, and Casamino acids.

Amino Acids↗

PubMed2001

Involvement of N-methyl-D-aspartic acid receptor activation in oxytocin and vasopressin release after osmotic stimuli in rats.

The present study aimed to examine roles of N-methyl-D-aspartic acid (NMDA) receptors in oxytocin and vasopressin release after osmotic stimuli. A noncompetitive NMDA receptor antagonist, MK-801 (0.2 mg/kg body weight, i.p.), significantly decreased plasma concentrations of oxytocin and vasopressin after hypertonic saline injection (0.3 or 0.6 M NaCl, i.p., 20 ml/kg). By contrast, oxytocin release induced by injection of cholecystokinin octapeptide (20 microg/kg, i.p.) was not significantly changed by MK-801. Hypertonic saline injection increased the number of cells expressing Fos in the supraoptic nucleus and in the regions anterior and ventral to the third ventricle (AV3V) regions [the organum vasculosum of the lamina terminalis (OVLT) and median preoptic nucleus]. MK-801 decreased the number of cells expressing protein in these areas after hypertonic saline injection. A microdialysis method showed that a hypertonic saline injection (0.6 M NaCl, 20 ml/kg, i.p.) facilitated glutamic acid release in and near the OVLT. The results support the view that NMDA receptor in the AV3V region modulates in a facilitative fashion the AV3V inputs to the supraoptic neurosecretory neurones.

Animals↗

PubMed2001

Facilitation of Ca2+ store-dependent noradrenaline release after an N-methyl-D-aspartate receptor antagonist in the rat supraoptic nucleus.

We examined the role of N-methyl-d-aspartate (NMDA) receptors in the control of noradrenaline release in the supraoptic nucleus (SON) using a microdialysis method in urethane-anaesthetized rats. Local application of 0.5 mm NMDA into the SON by retrodialysis decreased noradrenaline content in the dialysate from the SON. On the other hand, MK-801, a channel blocker of NMDA receptors, or D(-)2-amino-5-phosphonopentanoic acid (AP-5), a competitive NMDA receptor antagonist, increased the basal noradrenaline content. Tetrodotoxin did not completely block the noradrenaline increase after NMDA antagonists. Infusion of Ca2+-free solution containing Ni2+ and Cd2+, or a mixture of omega-agatoxin IVA and omega-conotoxin GVIA, voltage-sensitive Ca2+ channels blockers, did not block noradrenaline increase after AP-5, but blocked noradrenaline increase after high K+. Infusion of intracellular Ca2+ blockers, thapsigargin or TMB-8, impaired noradrenaline increase after AP-5 but not that after high K+. These data are consistent with the hypothesis that activation of an NMDA receptor inhibits an intracellular Ca2+ store-dependent noradrenaline release from nerve terminals in the SON.

Adrenergic Uptake Inhibitors↗