Biomedical subjects

M Katsura

Publications and source records attributed to M Katsura.

At least 19 recordsLinked to original sources

PubMed2001

Withdrawal from nicotine facilitates diazepam binding inhibitor mRNA expression in mouse cerebral cortex.

Changes in diazepam binding inhibitor (DBI) mRNA expression after withdrawal from nicotine were examined. Withdrawal from nicotine Increased DBI mRNA expression in cerebral cortices derived from nicotine-dependent mice and in the neurons continuously exposed to nicotine (0.1 microM). These results indicate that withdrawal from nicotine after its long-term exposure induces steep increase of DBI mRNA expression as reported previously in ethanol- and morphine-dependent animals.

Animals↗

PubMed2001

Manipulation of selective cell adhesion and growth by surface charges of electrically polarized hydroxyapatite.

Adherence of cells to a surface, such as a biomaterial surface, can be significantly influenced by the surface charge on that material. The applicability of electrically charged hydroxyapatite ceramics to selective cell adhesion was examined, and we show that polarized hydroxyapatite has significant effects on cell growth and adhesion. The surface charge applied to polarized hydroxyapatite promotes (i) enhanced colony formation of osteoblast-like cells, (ii) activation of gap junctions, and (iii) specific orienting of neuroblastoma cells. These findings will be of great utility and have significance in applications of tissue engineering, for example, in potential treatments for osteoporosis.

Cell Adhesion↗

PubMed2001

Suppression of Ca2+ influx through L-type voltage-dependent calcium channels by hydroxyl radical in mouse cerebral cortical neurons.

In the present study, we investigated the effect of hydroxyl radical (.OH) produced by the Fenton reaction with FeSO(4) to H(2)O(2) on Ca2+ influx by measuring [(45)Ca2+] influx into mouse cerebral cortical neurons in primary culture.OH formed from 3 microM FeSO(4) and 0.01 microM H(2)O(2) significantly reduced 30 mM KCl-induced [(45)Ca2+] influx and this reduction was abolished by .OH scavengers such as N,N'-dimethylthiourea and mannitol. Nifedipine (1 microM), an inhibitor for L-type voltage-dependent Ca2+ channels (VDCCs) showed no additive effect on the reduction of the 30 mM KCl-induced [(45)Ca2+] influx, while the inhibitors for P/Q- and N-type VDCCs showed further suppression of the KCl-induced [(45)Ca2+] influx even in the presence of .OH. Bay k 8644, an activator of L-type VDCCs, dose-dependently stimulated [(45)Ca2+] influx, and this stimulation disappeared in the presence of nifedipine. Similarly, .OH also suppressed significantly [(45)Ca2+] influx induced by Bay k 8644. These inhibitory actions of .OH on the KCl- and Bay k 8644-induced [(45)Ca2+] influx were completely abolished by .OH scavengers. These results indicate that .OH has the activity to suppress Ca2+ influx through L-type VDCCs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2001

Improved nasal bioavailability of elcatonin by insoluble powder formulation.

The bioavailability of elcatonin (ECT) via the nasal route was investigated with a powder dosage form utilizing water-insoluble calcium carbonate (CaCO(3)) in comparison with the liquid dosage form. Total radioactivity and the radioactivity of intact [3H]ECT were measured to evaluate the nasal absorption in vivo and the nasal mucosal transport in vitro. The systemic bioavailability of both total radioactivity and intact [3H]ECT following intranasal administration of the powder formulation in rats was significantly greater than in the case of the liquid formulation. In contrast, similar permeability of ECT across excised rabbit nasal mucosa was seen for both formulations, and was close to that of [14C]inulin, suggesting that the ECT transport is predominantly paracellular in each case. However, the powder formulation significantly prolonged the residence time of [3H]ECT in the rat nasal cavity, compared with the liquid formulation. We conclude that the powder formulation utilizing CaCO(3) improves the nasal bioavailability by increasing the residence time of ECT in the nasal cavity and is likely to be effective in increasing systemic drug delivery.

Administration, Intranasal↗

PubMed2001

NMDA receptor activation enhances diazepam binding inhibitor and its mRNA expressions in mouse cerebral cortical neurons.

Effects of N-methyl-D-aspartate (NMDA) on diazepam binding inhibitor (DBI) and its mRNA expression in mouse cerebral cortical neurons were examined. A significant increase in DBI mRNA expression was observed 1 day after the exposure to 0.1 microM NMDA and the maximal expression occurred 2 days after the exposure, whereas transient exposure to 0.1 microM NMDA for 15 min, 1 and 3 h produced no changes in the expression. Similarly, no changes in the expression were found by the concomitant exposure to NMDA and MK-801, a NMDA receptor antagonist, for 72 h subsequent to the incubation with NMDA alone for 3 h. Such NMDA-induced increases in DBI mRNA expression were dose-dependently inhibited by MK-801. Moreover, neuronal DBI content significantly increased by treatment with NMDA, which was completely abolished by MK-801. These results indicate that continuous activation of NMDA receptors is an essential factor for increasing DBI expression in the neurons.

Animals↗

PubMed2001

Study on local structure around Ce and Gd atoms in CeO2-Gd2O3 binary system.

X-ray absorption spectra near Ce and Gd K-edges of binary oxide of Ce(x)Gd(1-x)O(3+x)/2 (0 < or = x < or = 0.5) in C-type structure solid solution were measured by use of the beamline BL01B1 at SPring-8. Interatomic distances between rare-earth and oxygen atoms. R(Gd-O) and R(Ce-O), were evaluated with the extended x-ray absorption fine structure analysis and found to increase with x. R(Gd-O) was larger than R(Ce-O) by about 0.1 A. Metal-oxygen distances estimated as their linear combinations, xR(Ce-O) + (1-x)R(Gd-O), well agreed with those determined by X-ray diffraction.

Journal Article↗

PubMed2001

Alterations in cerebral diazepam binding inhibitor expression in drug dependence: a possible biochemical alteration common to drug dependence.

Mechanisms for formation of drug dependence and expression of withdrawal syndrome have not fully clarified despite of huge accumulation of experimental and clinical data at present. Several clinical features of withdrawal syndrome are considered to be common among patients with drug dependence induced by different drugs of abuse. One of them is anxiety. Recent investigations have revealed that diazepam binding inhibitor (DBI), a peptide consisting of 87 amino acids with molecular weight of about 10 kDa, serves as an inverse agonist for benzodiazepine (BZD) receptors with endogenously anxiogenic potential. These lines of data suggest that cerebral DBI expression in brain may participates in formation of drug dependence and/or emergence of withdrawal syndrome. Based on this working hypothesis, we have examined DBI expression in the brain derived from mice depended on alcohol (ethanol), nicotine, and morphine to investigate functional relationship between cerebral DBI expression and drug dependence. Cerebral DBI expression significantly increases in animals with drug dependence induced by these drugs, and in the cases of nicotine- and morphine-dependent mice concomitant administration of antagonists for nicotinic acetylcholine and opioid receptors, respectively, abolished the increase. Abrupt cessation of administration of drugs facilitated further increase in DBI expression. Therefore, these alterations in DBI expression have close relationship with formation of drug dependence and/or emergence of withdrawal syndrome, and are considered to be a common biochemical process in drug dependence induced by different drugs of abuse. Finding and elucidation of mechanisms for common biochemical alterations among drug dependence may provide a clue to clarify mechanisms for formation of drug dependence and/or emergence of withdrawal syndrome.

Alcoholism↗

PubMed2001

Nitric oxide and peroxynitrite as factors to stimulate neurotransmitter release in the CNS.

This review summarizes the stimulatory potentials of NO and peroxynitrite (OONO-) on neurotransmitter release in the central nervous system. Exogenous and endogenous NO stimulates to release neurotransmitter. NO synthesized intracellularly diffuses out through neuronal membrane and acts on the outer side of membrane to depolarize neuronal membrane, which triggers neurotransmitter release. NO-induced release of neurotransmitters is mediated by Ca2+-dependent and -independent processes. The latter process is operated by reverse process of the Na+-dependent carrier-mediated neurotransmitter uptake system or by unknown mechanisms. Ca2+-dependent release of neurotransmitter occurs in part subsequent to increase in Ca2+ influx via VDCCs, although N-type VDCCs may not involve in this action of NO because of suppression of Ca2+ influx through N-type VDCCs by NO. Participation of cGMP formation by NO on neurotransmitter release is controversial. A superoxide scavenger, Ca2+, Zn(2+)-superoxide dismutase, abolishes NO-induced neurotransmitter release and synthesized OONO- induces neurotransmitter release, indicating that OONO- participates in NO-evoked neurotransmitter release.

Animals↗

PubMed2001

Peroxynitrite affects Ca2+ influx through voltage-dependent calcium channels.

The effect of peroxynitrite (OONO-) on voltage-dependent Ca2+ channels (VDCCs) was examined by measuring [45Ca2+] influx into mouse cerebral cortical neurones. OONO- time- and dose-dependently increased [45Ca2+] influx and this increase was abolished by manganese (III) tetrakis (4-benzoic acid) porphyrin, a scavenger for OONO-. Inhibition of cyclic GMP (cGMP) formation did not alter the OONO(-)-induced [45Ca2+] influx. OONO-, as well as 30 mm KCl, significantly increased fluorescence intensity of cell-associated bis-(1,3-dibutylbarbituric acid) trimethine oxonol (bis-oxonol). Tetrodotoxin and membrane stabilizers such as lidocaine dose-dependently suppressed OONO(-)-induced [45Ca2+] influx. Although each of 1 microM nifedipine and 1 microM omega-agatoxin VIA (omega-ATX) significantly inhibited the OONO(-)-induced [45Ca2+] influx and the concomitant presence of these agents completely abolished the influx, 1 microM omega-conotoxin GVIA (omega-CTX) showed no effect on the influx. On the other hand, OONO- itself reduced 30 mM KCl-induced [45Ca2+] influx to the level of [45Ca2+] influx induced by OONO- alone, and the magnitude of this reduction was as same as that of KCl-induced [45Ca2+] influx by omega-CTX. These results indicate that OONO- increases [45Ca2+] influx into the neurones through opening P/Q- and L-type VDCCs subsequent to depolarization, and inhibits the influx through N-type VDCCs.

Anesthetics, Local↗

PubMed2001

Recent research on alcohol tolerance and dependence.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hiroshi Suwaki and Harold Kalant. The presentations were (1) Influence of ADH genotypes on acute alcohol withdrawal syndrome in Japanese, by Susumu Higuchi; (2) Use of genetic analyses to refine phenotypes related to alcohol tolerance and dependence, by John C. Crabbe; (3) Neurochemical basis for alcohol dependence, by Seitaro Ohkuma and Masashi Katsura; (4) Adenylyl cyclase and development of tolerance to addictive drugs, by Masami Yoshimura; (5) Tolerance in rat lines selectively bred for alcohol preference, by Robert C. Stewart and Ting-Kai Li; and (6) Ethanol reinforcement, dependence, and vulnerability to relapse: Interactions between neuroadaptive and conditioning factors, by Friedbert Weiss.

Alcohol Dehydrogenase↗

PubMed2001

[Functional involvement of cerebral diazepam binding inhibitor (DBI) in the establishment of drug dependence].

Mechanisms for formation of drug dependence and emergence of withdrawal syndrome are not yet fully understood despite of a huge accumulation of experimental and clinical data. Several clinical features of withdrawal syndrome are considered to be common (i.e., anxiety) among patients with drug dependence induced by different drugs of abuse. In this review, we have discussed the possibility of the functional involvement of diazepam binding inhibitor (DBI), an endogenous neuropeptide for benzodiazepine receptors with endogenously anxiogenic potential, in the development of drug dependence and emergence of its withdrawal symptom. The levels of DBI protein and its mRNA significantly increased in the brain derived from mice dependent on alcohol (ethanol), nicotine and morphine, and abrupt cessation of these drugs facilitated further increase in DBI expression. In the cases of nicotine- and morphine-dependent mice, concomitant administration of antagonists for nicotinic acetylcholine and opioid receptors, respectively, abolished the increase in DBI expression. Therefore, these alterations in DBI expression have a close relationship with formation of drug dependence and/or emergence of withdrawal syndrome and are considered to be a common biochemical process in drug dependence induced by different drugs of abuse.

Animals↗

PubMed2000

Mechanism for increase in expression of cerebral diazepam binding inhibitor mRNA by nicotine: involvement of L-type voltage-dependent calcium channels.

We investigated the mechanisms underlying the increase in diazepam binding inhibitor (DBI) and its mRNA expression induced by nicotine (0.1 microM) exposure for 24 h using mouse cerebral cortical neurons in primary culture. Nicotine-induced (0.1 microM) increases in DBI mRNA expression were abolished by hexamethonium, a nicotinic acetylcholine (nACh) receptor antagonist. Agents that stabilize the neuronal membrane, including tetrodotoxin (TTX), procainamide (a Na(+) channel inhibitor), and local anesthetics (dibucaine and lidocaine), dose-dependently inhibited the increased expression of DBI mRNA by nicotine. The nicotine-induced increase in DBI mRNA expression was inhibited by L-type voltage-dependent Ca(2+) channel (VDCC) inhibitors such as verapamil, calmodulin antagonist (W-7), and Ca(2+)/calmodulin-dependent protein kinase II (CAM II kinase) inhibitor (KN-62), whereas P/Q- and N-type VDCC inhibitors showed no effects. In addition, nicotine exposure for 24 h induced [3H]nicotine binding to the particulate fractions of the neurons with an increased B(max) value and no changes in K(d). Under these conditions, the 30 mM KCl- and nicotine-induced 45Ca(2+) influx into the nicotine-treated neurons was significantly higher than those into non-treated neurons. These results suggest that the nicotine-stimulated increase in DBI mRNA expression is mediated by CAM II kinase activation resulting from the increase in intracellular Ca(2+) through L-type VDCCs subsequent to the neuronal membrane depolarization associated with nACh receptor activation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2000

Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency.

Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder of fatty acid oxidation caused by defective cellular carnitine transport. The disease is characterized by metabolic derangement simulating Reye's syndrome, hypoglcaemia, progressive cardiomyopathy and skeletal myopathy. Recently, it was shown that SCD is caused by mutations in the organic cation/carnitine transporter OCTN2 (SLC22A5). We report two novel mutations, W283R and V446F, which are both missense mutations in an affected infant. In vitro expression studies demonstrated that both are actually function-loss mutations with virtually no uptake activity. This is the first report of compound heterozygosity for two missense mutations in a patient with SCD. Hum Mutat 15:118, 2000.

Carnitine↗

PubMed1998

Removal of hydroxyl radical facilitates Ca2+-dependent [3H]GABA release by peroxynitrite.

We investigated mechanisms for enhancement of peroxynitrite (OONO-; 5 microM)-evoked [3H] gamma-aminobutyric acid (GABA) release. Hydroxyl radical scavengers such as N,N'-dimethylthiourea (DMTU), mannitol, and uric acid, significantly increased OONO--evoked [3H]GABA release, whereas urea showed no effects on the release. Removal of Ca2+ from incubation buffer abolished the enhancement of the release by DMTU, although DMTU showed no effects on the basal release with and without Ca2+ in extracellular space. These results indicate that hydroxyl radical scavengers facilitate OONO--evoked [3H]GABA release dependent on Ca2+.

Animals↗

PubMed1998

Overexpression of CD44 variants 6 and 7 in human endometrial cancer.

OBJECTIVES: The expression of CD44 V6, V7, and V10 in normal endometrium and endometrial cancer was compared. METHODS: Using reverse transcription polymerase chain reaction (RT-PCR) blot analysis, the expression of mRNA containing CD44 V6, V7, and V10 was determined in 19 normal endometrium and 27 endometrial cancer samples. Immunohistochemical staining of CD44 V6 and V7 was performed in the same samples. RESULTS: In RT-PCR analysis, the CD44 variant forms containing V6 and V7 exons were expressed in 96 and 93% of endometrial cancer tissues, respectively. These proportions were significantly higher than those in normal endometrium (V6, 63%; V7, 58%) (P < 0.01). CD44 V10 was expressed in 96% of endometrial cancers and 89% of normal endometrial samples. In immunohistochemical staining, CD44 V6 and V7 were detected in 48 and 61% of endometrial cancers and in 26 and 42% of normal endometrial samples, respectively. Neither of these differences was significant. No correlation was found between the expression of CD44 variants and any clinicopathological features. CONCLUSION: CD44 V6 and V7 were expressed in a significantly larger proportion of endometrial cancers than normal endometrial samples. However, they were also expressed in a considerable proportion of normal endometria. These findings suggest that CD44 V6 and V7 play roles in normal endometrial function and overexpression of CD44 V6 and V7 is not related to the metastatic potential of endometrial cancer.

Adult↗

PubMed1998

Enhancement of peroxynitrite-evoked acetylcholine release by hydroxyl radical scavengers from mouse cerebral cortical neurons.

We investigated the effects of hydroxyl radical scavengers on peroxynitrite (OONO-)-evoked acetylcholine (ACh) release from mouse cerebral cortical neurons. N,N'-dimethylthiourea, a hydroxyl radical scavenger, dose-dependently increased OONO(-)-evoked ACh release. Other hydroxyl radical scavengers such as uric acid and mannitol, also enhanced OONO(-)-evoked ACh release, although these enhancing effects were not found in the absence of OONO-. In addition, OONO(-)-induced [45Ca2+]influx was significantly facilitated by the scavengers, whereas no effects of the scavengers on [45Ca2+]influx was observed in the absence of OONO-. These results indicate that hydroxyl radical scavengers enhance OONO(-)-evoked ACh release via the facilitation of OONO(-)-induced [45Ca2+]influx.

Acetylcholine↗

PubMed1998

Functional involvement of benzodiazepine receptors in ethanol-induced increases of diazepam binding inhibitor (DBI) and its mRNA in the mouse brain.

We have attempted to clarify the mechanisms for alcohol (EtOH)-induced elevation of diazepam binding inhibitor (DBI) mRNA and to investigate whether the increase in DBI mRNA is paralleled with that in DBI using EtOH-treated mice and primary cultured neurons. Both the DBI content and the expression of DBI mRNA were elevated in the cerebral cortex of EtOH-inhaled and -withdrawn mice. Simultaneous administration of flunitrazepam (FLN) and Ro15-1788 with EtOH vapor completely abolished the EtOH-induced elevation of DBI mRNA. In addition, the exposure of the neurons for 3 days significantly elevated the expression of DBI mRNA, which was completely inhibited by concomitant exposure of FLN, Ro15-4513 and Ro-15-1788 with EtOH, while muscimol and bicuculline showed no effects on the EtOH-induced increase of DBI mRNA expression. These results indicate that functional interaction between EtOH and benzodiazepine (BDZ) receptors is a critical role in the increased expression of DBI mRNA.

Administration, Inhalation↗

PubMed1998

Multiple actions of nitric oxide on voltage-dependent Ca2+ channels in mouse cerebral cortical neurons.

We investigated the effects of nitric oxide (NO) on voltage-dependent Ca2+ channels (VDCCs) by examining [45Ca2+]influx into mouse cerebral cortical neurons. S-nitroso-N-acetylpenicillamine (SNAP) induced a dose-dependent increase in [45Ca2+]influx, which was completely abolished by hemoglobin, tetrodotoxin and dibucaine. The NO-induced [45Ca2+influx was significantly inhibited by verapamil and omega-agatoxin VIA (omega-AGX), whereas omega-conotoxin GVIA (omega-CTX) had no effects on the NO-induced [45Ca2+]influx. KCl (30 mM) stimulated [45Ca2+]influx, and verapamil, omega-CTX and omega-AGX reduced the KCl-induced [45Ca2+]influx by about 40, 26 and 34%, respectively, indicating that the neurons used here possess L-, N- and P-typed VDCCs. SNAP itself reduced KCl-induced [45Ca2+]influx by about 28.5%. In the presence of both KCl and SNAP, omega-CTX showed no effects on the influx, while verapamil and omega-AGX significantly inhibited the influx and the concomitant presence of verapamil and omega-AGX completely abolished the influx. These results indicate that NO induces [45Ca2+] influx via the opening of L- and P-typed VDCCs subsequent to neuronal membrane depolarization and that NO itself inhibited the function of N-typed VDCC in the cerebral cortical neurons.

Animals↗