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S Shibata

Publications and source records attributed to S Shibata.

At least 19 recordsLinked to original sources
PubMed1992

Ischemia-induced impairment of 2-deoxyglucose uptake and CA1 field potentials in rat hippocampal slices: protection by 5-HT1A receptor agonists and 5-HT2 receptor antagonists.

Various in vitro models have been developed to study ischemia and/or hypoxia. In the present experiment, we examined whether hypoxia/hypoglycemia (ischemia) in rat hippocampal slices reduced the 2-deoxyglucose (2-DG) uptake and CA1 field potentials evoked by stimulation of Schaffer collaterals. Autoradiograms revealed that ischemia for 15 or 20 min reduced 2-DG uptake in the stratum radiatum of the CA1 and the dentate gyrus. Similarly, the CA1 field potentials of slices exposed to ischemia for 15 and 20 min decreased by about 70 and 90% after a 6-h washout. In the second experiment, we evaluated the neuroprotective effect of the 5-HT1A receptor agonists 8-OH-DPAT and buspirone, and the 5-HT2 receptor antagonists cyproheptadine, mianserin and ketanserin on deficits of 2-DG uptake and Schaffer-CA1 field potentials induced by ischemia. The 5-HT1A receptor agonists and 5-HT2 receptor antagonists exhibited significant neuroprotective actions against ischemia-induced deficits. Therefore, impairments of 2-DG uptake and CA1 field potentials induced by ischemia may be good markers of ischemia-induced functional deficits. The attenuating action of 5-HT1A receptor agonists and 5-HT2 receptor antagonists were assessed using this model of ischemia.

Animals↗
PubMed1992

Effect of substance P on circadian rhythms of firing activity and the 2-deoxyglucose uptake in the rat suprachiasmatic nucleus in vitro.

The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many circadian rhythms in mammals. Although substance P (SP) fibers from retina are found to terminate the SCN, the physiological role of this peptide is uncertain. The 2-deoxyglucose (2-DG) uptake and firing activity in the SCN show a robust circadian change. SP causes an increase in 2-DG uptake by SCN during the subjective night but not during subjective day. SP-induced increase in 2-DG uptake is blocked by co-treatment with the SP receptor antagonist, spantide. Treatment with SP produces phase shifts of circadian rhythm in spontaneous neural activity in SCN neurons with a phase-response curve that is similar to the effect of light pulses to animals under constant darkness. SP-induced phase change is also blocked by pretreatment with spantide. SP-induced increase in 2-DG uptake and phase changes in firing activity occur only during subjective night, at circadian times when photic phase shifting of activity occurs. The present results suggest that SP may be an important transmitter for conveying environmental light-dark information from retina to the SCN.

Action Potentials↗
PubMed1992

Neuroprotective effect of protein kinase C inhibitors on oxygen/glucose free-induced decreases in 2-deoxyglucose uptake and CA1 field potentials in rat hippocampal slices.

Staurosporine, a protein kinase C inhibitor, was found to produce a neuroprotective effect against an ischemic insult in both gerbils and rats in vivo. We have demonstrated that rat hippocampal slices exposed to oxygen/glucose-free medium showed decreases in 2-deoxyglucose (2-DG) uptake and CA1 field potentials elicited by the stimulation of Schaffer collaterals. Therefore we examined the effect of protein kinase C inhibitors on oxygen/glucose free-induced impairments of 2-DG uptake and CA1 field potentials. Pretreatment with staurosporine, K252a and H-7 attenuated decreases in 2-DG uptake and CA1 field potentials. Treatment with phorbol ester, a protein kinase C activator, for a long period (90 min) was found to induce a down-regulation of protein kinase C activity. Therefore we examined the effect of pretreatment with phorbol ester for 90 min on oxygen/glucose free-induced decreases in 2-DG uptake and CA1 field potentials. These decrements were not attenuated by 5-min treatment with phorbol ester but were attenuated by 90-min treatment. The present results suggest that the treatment which decreases protein kinase C activity shows a neuroprotective action against oxygen/glucose free-induced deficits of metabolic and synaptic activity in hippocampal slices.

Alkaloids↗
PubMed1992

Assessment of the role of adrenoceptor function in ischemia-induced impairment of 2-deoxyglucose uptake and CA1 field potential in rat hippocampal slices.

The release of catecholamines, dopamine and noradrenaline has been suggested to play a role in mediating ischemic damage in susceptible brain regions, the hippocampus and striatum. We now provide evidence that suggests a role for adrenoceptors in the deficit of 2-deoxyglucose uptake and CA1 field potential induced in hippocampal slices by hypoxia/hypoglycemia (ischemia). Treatment with alpha 1- or beta-adrenoceptor agonists or cAMP potentiated an ischemia-induced decline of both 2-deoxyglucose uptake and CA1 field potential in hippocampal slices, whereas alpha 1- or beta-adrenoceptor antagonists, or alpha 2-adrenoceptor agonists produced a remarkable neuroprotective action against these deficits. The results indicate that stimulation of adrenoceptors may play a detrimental role in the development of ischemic damage, and suggest a neuroprotective action for adrenoceptor antagonists, which may lessen the functional deficits induced by ischemia.

Action Potentials↗
PubMed1992

Effect of muscarinic cholinergic drugs on ischemia-induced decreases in glucose uptake and CA1 field potentials in rat hippocampus slices.

To clarify the role of muscarinic acetylcholine receptors in the hypoxia/hypoglycemia (ischemia)-induced functional deficit in hippocampal neurons, we examined the effect of cholinergic drugs on ischemia-induced impairments of glucose uptake and CA1 field potentials in hippocampus slices. Muscarinic receptors were subdivided into M1 (high affinity for pirenzepine) and M2 (low affinity for pirenzepine) subtypes. The M1 receptor subtype is coupled to an increase in phosphoinositide hydrolysis and the M2 receptor subtype is associated with inhibition of adenylate cyclase. The greater potency of carbachol in stimulating phosphoinositide hydrolysis resulted in exacerbated ischemia-induced deficits. Treatment with the muscarinic receptor antagonists scopolamine and pirenzepine (M1 receptor-selective antagonist) had a strong dose-dependent protective effect against ischemia-induced deficits. Oxotremorine and McN-A-343, weak stimulators of phosphoinositide hydrolysis and strong inhibitors of adenylate cyclase, had a weak neuroprotective action against ischemia-induced deficits. These results suggest that stimulation of M1 muscarinic receptors coupled with an increase in phosphoinositide hydrolysis may play a facilitatory role in ischemia-induced deficits. Stimulation of M2 muscarinic receptors may play an inhibitory role in ischemia-induced neuronal deficits.

Acetylcholine↗
PubMed1992

A neuroprotective effect of adenosine A1-receptor agonists on ischemia-induced decrease in 2-deoxyglucose uptake in rat hippocampal slices.

The effects of adenosine (A) receptor agonists on ischemia-induced impairment of 2-deoxyglucose (2-DG) uptake by rat hippocampal slices was evaluated. Hippocampal slices were exposed to 20-min hypoxia + hypoglycemia (ischemia) and then returned to oxygenated and glucose-containing Krebs-Ringer solution for 6 h. Ischemia reduced 2-DG uptake in the hippocampal slices. The ischemia-induced reduction in 2-DG uptake was attenuated by pretreatment with A1 receptor agonists but not with A2 receptor agonists. 8-Phenyltheophylline, an A1 receptor antagonist, exacerbated the ischemia-induced decrease. The A1 receptor agonist-induced neuroprotective effect was blocked by co-treatment with 8-phenyltheophylline. The present study suggests that the A1 receptor-mediated function has a protective role in ischemia-induced decreases in glucose metabolism in hippocampal slices.

Adenosine↗
PubMed1992

An in vitro circadian rhythm of protein synthesis in the rat suprachiasmatic nucleus under tissue culture conditions.

Because inhibitors of protein synthesis produce changes in the circadian rhythm of wheel-running activity in rodents, we examined the circadian changes of in vitro protein synthesis by the rat suprachiasmatic nucleus (SCN). We demonstrated a robust circadian rhythm of [14C]leucine incorporation as well as [3H]2-deoxyglucose (2DG) uptake by the SCN. The peak time of 2DG uptake was around circadian time 6-9 h (CT6-CT9). In contrast to 2DG uptake, the maximum rate of leucine incorporation occurred around CT22-CT0. Thus, the leucine incorporation rate preceded 2DG uptake by 6-9 h. Leucine incorporation was inhibited by protein synthesis inhibitors, but not by tetrodotoxin. Since a robust circadian rhythm of leucine incorporation by the SCN was detected in vitro by using our method, this procedure may be useful to study the circadian clock function of the SCN.

Animals↗
PubMed1992

Effects of inhibitory and excitatory drugs on the metabolic rhythm of the hamster suprachiasmatic nucleus in vitro.

In order to elucidate the role of excitatory and inhibitory transmitters within the suprachiasmatic nucleus (SCN) in the circadian change of 2-deoxyglucose (2-DG) uptake in this nucleus, the effects of 8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT), muscimol, flurazepam, pentobarbital and glutamate on uptake of 2-DG by hamster SCN were examined in hypothalamic slice preparations. 2-DG uptake in the SCN was high during the subjective day and low during the subjective night. The high uptake of 2-DG in the SCN during the daytime was inhibited by the superfusion of 8-OH-DPAT, muscimol, flurazepam and pentobarbital in a dose-dependent manner, but the low uptake of 2-DG during the night was unaffected. The low uptake during the night was significantly increased by treatment with glutamate, whereas 2-DG uptake during the day was unaffected. In contrast to the above results, 20 mM KCl and 1 microM tetrodotoxin increased and decreased 2-DG uptake during both the day and night, respectively. The present results strongly suggest that agonists of 5-HT1A receptors and GABAA-benzodiazepine-barbiturate complex receptors regulate the function of the SCN through their inhibitory action on 2-DG uptake during the day, and that glutamate also regulates SCN function through it stimulatory action on 2-DG uptake during the night.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Phase-resetting effect of 8-OH-DPAT, a serotonin1A receptor agonist, on the circadian rhythm of firing rate in the rat suprachiasmatic nuclei in vitro.

The 5-HTergic neurons in the mesencephalic raphe nuclei provide a robust projection to the hypothalamic suprachiasmatic nucleus (SCN), the site of a putative neuronal circadian pacemaker. Although it has been suggested that 5-HT neurons may play a role in the circadian timing system, this role has not yet been specified. Prosser et al. (Brain Res., 534 (1990) 336-339) reported that 1 h treatments with quipazine induce robust phase shifts in vitro, and that this effect depends upon the circadian time of treatment. However, quipazine is a non-specific 5-HT agonist. Besides, it is reported that the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetraline hydrobromide (8-OH-DPAT) affected a circadian rhythm of hamster wheel-running activity. In the present study we investigated whether the 5-HT1A agonist 8-OH-DPAT can reset the phase of the SCN clock when it is isolated in vitro. The present results show that 1 h treatments with 8-OH-DPAT induce robust phase advances in vitro when it was administered during the subjective day. This result suggests that 5HT1A receptor functioning may play a role in modulating the phase of SCN clock, especially during the subjective day.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Morphological and functional development of the suprachiasmatic nucleus in transplanted fetal hypothalamus.

The development of the suprachiasmatic nucleus (SCN) in fetal rat hypothalamus transplanted to the adult brain was studied using morphological and functional methods. Anterior hypothalamic tissue was transplanted into the third ventricle, lateral ventricle or subarachnoid space of intact, adult hosts from E17 fetuses. These transplants developed the cytoarchitectonic and immunohistochemical staining characteristics of SCN, clusters of parvocellular neurons expressing vasopressin- and vasoactive intestinal polypeptide-like immunoreactivity in adjacent cellular populations, irrespective of the exact location of the transplanted tissue in the host brain. The functional status of the transplants placed in the rostral third ventricle and the foramen of Monroe was analyzed and compared to host SCN using in vitro recording of neuronal firing rate and measurement of metabolism using the 2-deoxyglucose (2-DG) technique. During subjective day, neuronal firing rates and 2-DG uptake were high in discrete cell groups within the transplants which were subsequently demonstrated to exhibit the cytoarchitectonic and immunohistochemical characteristics of SCN. The firing rates and 2-DG uptake in these areas were lower during the subjective night. This pattern of activity closely resembles that of the intact SCN. In contrast, neither transplanted anterior hypothalamic area, lacking an identifiable SCN-like structure, nor posterior hypothalamic area showed day-night differences in firing rate or 2-DG uptake. These observations indicate that SCN transplanted into intact adult hosts exhibits morphological and functional differentiation nearly identical to the host and that the transplanted SCN maintains circadian function which is probably entrained to the host SCN.

Action Potentials↗
PubMed1992

Excitatory effect of N-methyl-D-aspartate and kainate receptor on the 2-deoxyglucose uptake in the rat suprachiasmatic nucleus in vitro.

The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many circadian rhythms in mammals. The previous findings indicate the excitatory amino acid (EAA) receptors play an important role in the transmission of light information from the retina to the circadian clocks. The 2-deoxyglucose (2DG) uptake shows a robust circadian change; high uptake during subjective day and low uptake subjective night. To determine whether EAA agonists regulate 2DG uptake in the SCN, we have measured 2DG uptake in the rat SCN in vitro. We report that, during the subjective night, glutamate, N-methyl-D-aspartate (NMDA) and kainic acid (KA) cause an increase in 2DG uptake and that NMDA- or KA-induced increase of 2DG uptake is blocked by co-treatments with competitive and non-competitive NMDA or KA receptor antagonists. EAA receptor agonist-induced increase in 2DG uptake occurs only during subjective night, at circadian times when photic phase shifting of activity occurs. Taken together, those data suggest that EAA may be an important transmitter of light information from retina to the SCN.

Animals↗
PubMed1992

Effects of 5-HT1A receptor agonists on the circadian rhythm of wheel-running activity in hamsters.

The effects of 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), buspirone and ipsapirone on wheel-running activity in hamsters were investigated in comparison with those of GABAA receptor agonist muscimol and benzodiazepine triazolam. Intraperitoneal administration of 8-OH-DPAT, buspirone, ipsapirone, muscimol and triazolam at circadian time (CT) 8 (CT 12; onset of activity) induced a significant phase advance of wheel-running activity under constant light conditions. However, administration of these drugs at other CT points did not induce phase changes. The administration of trifluoromethylphenylpiperazine (TFMPP), a 5-HT1B receptor agonist, at CT8 produced a small phase advance. The phase advance induced by 8-OH-DPAT was blocked by pretreatment with (-)-pindolol, a 5-HT1A receptor antagonist. In addition, 8-OH-DPAT, buspirone and SM3997 accelerated the rate of re-entrainment to an 8-h phase advance in the light-dark cycle. These observations suggest that 5-HT1A receptors in the brain participate in the regulation of the circadian rhythm of wheel-running activity in hamsters.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Structural analysis of the linkage region oligosaccharides and unsaturated disaccharides from chondroitin sulfate using CarboPac PA1.

Swarm rat chondrosarcoma cell cultures were metabolically labeled with [35S]sulfate, [3H]glucose, or [3H]glucosamine. Chondroitin sulfate chains were isolated from purified aggrecan using alkaline borohydride treatment and Superose 6 chromatography. Various linkage region oligosaccharide alditols were derived from these chains using sequential chondroitinase digestions (ABC lyase followed by ACII lyase). They were then further processed by mercuric acetate treatment, which removed the 4,5-unsaturated uronosyl residue from the nonreducing end of the linkage, and then beta-galactosidase digestion which liberated the 2 galactose residues from the xylitol reducing terminus. Alkaline phosphatase digestions were performed to verify the presence of phosphate esters. All linkage region structures were isolated and identified using a combination of Progel-TSK G2500 and CarboPac PA1 chromatography steps in conjunction with monosaccharide analyses. This study revealed that chondroitin sulfate chains from aggrecan synthesized by rat chondrosarcoma cells in vitro have the following properties: 1) three out of every four of their linkage regions carry a phosphate ester on xylose, 2) nearly three out of every five chains begin the repeating disaccharide region with an unsulfated first disaccharide unit, 3) nearly twice as many nonphosphorylated chains have a sulfated first disaccharide than their phosphorylated counterparts, and 4) the vast majority of these chains do not contain sulfated galactose in their linkage regions. This report also describes a borohydride reduction procedure to confer alkali stability to the 3-substituted, unsaturated disaccharides derived from chondroitinase digests of chondroitin sulfate. Furthermore, a CarboPac PA1 method is demonstrated that separates these reduced disaccharides with exceptional resolution.

Animals↗
PubMed1992

Supernumerary head of biceps brachii and branching pattern of the musculocutaneus nerve in Japanese.

Out of 546 upper limbs (273 cadavers), supernumerary heads of the biceps brachii were found in 75 limbs (13.7%) of 58 cadavers (21.3%). The form, origin, and insertion of the supernumerary heads, and branching pattern of the musculocutaneus nerve were studied. In addition, the dimensions of the heads were measured. In many cases, the supernumerary head arose from the humerus, between the insertion of the coracobrachialis and the upper part of the origin of the brachialis, and/or from the medial intermuscular septum. In a few cases, a supernumerary head arose from the tendon of the pectoralis major or the deltoid, or from the articular capsule, or from the crest of the greater tubercle. The supernumerary heads typically joined the common belly, or the aponeurosis of the biceps brachii. Some heads joined the belly of the long head or that of the short head. In the examination of the branching pattern of the musculocutaneus nerve, communication between the musculocutaneus nerve and the median nerve was found in 43 out of the 75 limbs (57.3%). The communicating branch ran from the musculocutaneus nerve to the median nerve in 24, from the median nerve to the musculocutaneus nerve in 12, in both directions in 5, or in another type of pattern in 2 out of 43 limbs. Sometimes a branch of the musculocutaneus nerve ran around a supernumerary head and then fused with the present trunk. The presence of a supernumerary head seemed to affect the course and branching of the musculocutaneus nerve.

Arm↗
PubMed1992

Clonal frequency analysis of B cells producing pathogenic anti-DNA antibody-associated idiotypes in systemic lupus erythematosus.

In order to identify the mechanism responsible for autoantibody production in systemic lupus erythematosus (SLE), B cell repertoires associated with anti-DNA idiotypes were explored by a limiting dilution analysis using Epstein-Barr virus (EBV) transformation methods and ELISA spot assays. The frequencies of B cell clones producing antibodies to DNA and to conventional antigens, tetanus toxoid, dinitrophenyl, or keyhole limpet hemocyanin were higher in active SLE compared to those in inactive SLE and in normal subjects. In addition, there was a disproportionate increase in anti-DNA antibody- and anti-DNA idiotype (Id)-producing clones at the precursor cell levels as well as at the mature cell level. On the other hand, numbers of anti-Id clones against anti-DNA-Id, termed 0-81 Id, were markedly increased at inactive stages of the disease but not at active stages. These were confirmed by serial studies in some patients with SLE. These results support a two-step mechanism for autoantibody production, in which initial polyclonal activation is followed by an antigen-driven process, and indicate an alteration of the precursor B cell repertoire in SLE, which may also associate with a preferential expansion of anti-DNA clones.

Antibodies, Antinuclear↗
PubMed1992

Mode of relaxing action of FK336, a new antianginal agent, in rabbit aorta.

1. FK336 (10(-6)-10(-4) M) inhibited contractile responses to norepinephrine (NE), KCl and Ca2+ in isolated rabbit aortas. 2. Relaxing effect of FK336 on KCl-response was inhibited by nitroglycerin (NG), but not by nifedipine or verapamil. 3. FK336 inhibited residual NE response and a subsequent Ca2+ response in Ca(2+)-free medium. FK336 did not affect the inositol monophosphate level. 4. Relaxing effect of FK336 on NE response was inhibited by methylene blue, NG, K(+)-channel inhibitors and acetylcholine (ACh), and potentiated by M&B 22,948 and theophylline. 8-Br cGMP and dibutyl cAMP had no effect. 5. FK336 increased cGMP level in rat aorta. 6. Potentiation of isoproterenol-relaxation by FK336 was inhibited by methylene blue. 7. The inhibitory effect of ACh on FK336-relaxation was eliminated by endothelium removal, nordihydroquaiaretic acid and guinacrine, but not by indomethacin. These treatments themselves did not affect FK336-relaxation. 8. The mode of vasorelaxing action of FK336 is discussed.

Acetylcholine↗