RESUMO
The Rare-RI Ring (R3) is a recently commissioned cyclotronlike storage ring mass spectrometer dedicated to mass measurements of exotic nuclei far from stability at Radioactive Isotope Beam Factory (RIBF) in RIKEN. The first application of mass measurement using the R3 mass spectrometer at RIBF is reported. Rare isotopes produced at RIBF-^{127}Sn, ^{126}In, ^{125}Cd, ^{124}Ag, ^{123}Pd-were injected in R3. Masses of ^{126}In, ^{125}Cd, and ^{123}Pd were measured whereby the mass uncertainty of ^{123}Pd was improved. This is the first reported measurement with a new storage ring mass spectrometry technique realized at a heavy-ion cyclotron and employing individual injection of the preidentified rare nuclei. The latter is essential for the future mass measurements of the rarest isotopes produced at RIBF. The impact of the new ^{123}Pd result on the solar r-process abundances in a neutron star merger event is investigated by performing reaction network calculations of 20 trajectories with varying electron fraction Y_{e}. It is found that the neutron capture cross section on ^{123}Pd increases by a factor of 2.2 and ß-delayed neutron emission probability, P_{1 n}, of ^{123}Rh increases by 14%. The neutron capture cross section on ^{122}Pd decreases by a factor of 2.6 leading to pileup of material at A=122, thus reproducing the trend of the solar r-process abundances. The trend of the two-neutron separation energies (S_{2n}) was investigated for the Pd isotopic chain. The new mass measurement with improved uncertainty excludes large changes of the S_{2n} value at N=77. Such large increase of the S_{2n} values before N=82 was proposed as an alternative to the quenching of the N=82 shell gap to reproduce r-process abundances in the mass region of A=112-124.
RESUMO
A rare earth doped form of ceria (CeO2) is of interest as a potential candidate for solid oxide fuel cells (SOFCs) because of its relatively high oxygen ion conductivity at temperatures below 600 °C. At the present time, computational chemistry has reached a certain maturity which allows the prediction of materials properties that are difficult to observe experimentally. However, understanding of the roles of dopants in the oxygen ion conduction in CeO2 is still incomplete for quantitatively reliable analysis due to the strong electron correlation of 4f electrons. In this study, density functional theory calculations with Hubbard U corrections are used to discuss ionic/covalent interactions in rare-earth-doped CeO2 and their consequences to oxygen ion conduction. This study suggests that the variable occupancy of empty 4f orbitals is important typically for early Ln elements to produce the covalent interactions that essentially affect the formation and migration of oxygen vacancies. This finding is important in understanding the factors responsible for oxygen ion diffusion in doped CeO2.
RESUMO
A theoretical model of plasmon and molecular luminescence induced by scanning tunneling microscopy using a molecule-covered tip on clean metal surfaces is developed. The effects of coupling between molecular exciton and interface plasmon on the luminescence spectra are investigated for variable energy of plasmon modes by means of the nonequilibrium Green's function method. It is found that spectral features arising from interference between the processes of energy absorption by the molecule and interface plasmons appear near the energy of the excitonic mode. For the energy of plasmon above (below) the energy of excitonic mode, an additional peak structure appears in the energy range slightly below (above) the energy of the excitonic mode. Prominent peak and dip structures observed in recent luminescence experiments are interpreted by the developed theory whereby its utility in the fields of plasmonics and nanophotonics is demonstrated.
Assuntos
Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Microscopia de Tunelamento/métodos , Modelos Químicos , Ressonância de Plasmônio de Superfície/métodos , Simulação por Computador , Transferência de Energia/efeitos da radiação , Luz , Nanopartículas Metálicas/ultraestrutura , Espalhamento de Radiação , Propriedades de Superfície/efeitos da radiaçãoRESUMO
The structural and electronic properties of bulk Pr(2)NiO(4+δ) (δ = 0 and 0.031) were analyzed using first-principles calculations based on the density functional theory (DFT) for application to electrode materials in solid-oxide fuel cells (SOFCs). Two structures of Pr(2)NiO(4) were analyzed: one in space group I4/mmm associated with the high temperature tetragonal (HTT) structure, and the other in Bmab with the low temperature orthorhombic (LTO) structure. The main difference between the two structures is the pronounced tilting of the nickelate octahedra found in the Bmab structure. Here, we will show that the difference in the electronic properties between the two structures, i.e. half-metallic for the I4/mmm structure and metallic for the Bmab structure, is attributed to the tilting of the nickelate octahedra. Furthermore, we found that the presence of interstitial O atoms at the Pr(2)O(2) bilayers is responsible for the tilting of the octahedra and thus is a dominant factor in the transition from the I4/mmm structure to the Bmab structure. These results would be of great significance to materials design related to the enhancement of O diffusivity in this material.
Assuntos
Modelos Químicos , Modelos Moleculares , Níquel/química , Praseodímio/química , Simulação por Computador , Condutividade Elétrica , Conformação MolecularAssuntos
Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Compostos de Metilmercúrio/toxicidade , Neurônios/efeitos dos fármacos , Selenito de Sódio/farmacologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Cerebelo/metabolismo , Quimioprevenção , Antagonismo de Drogas , Compostos de Metilmercúrio/farmacocinética , Neurônios/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND: Peroxisome proliferators-activated receptor gamma (PPAR gamma) is a nuclear hormone receptor that serves as a master regulator of adipocytes-specific genes contributing to adipocytes differentiation, susceptibility to obesity, and insulin sensitivity. The substitution of proline to alanine at codon 12 of the PPAR gamma2 gene (Pro12Ala polymorphism) is most frequently identified and the associations with diabetes, obesity, and other clinical parameters have been reported and discussed in several ethnic groups. Among native Javanese ethnicity, however, there is no report about this polymorphism. AIMS AND METHODS: Aims of this study were to estimate the allele frequency of the Pro12Ala polymorphism of PPAR gamma2 gene among native Javanese in Indonesia and to investigate the relationship between this polymorphism and obesity or diabetes. This study included 540 native Javanese subjects consisting of 337 diabetic patients and 203 normal glucose tolerance subjects. Both groups included totally 160 obese subjects (body mass index > or = 25 kg/m(2)). PCR-restriction fragment length polymorphism was used for the genotype determination. RESULTS: The allele frequency of Pro12Ala polymorphism in PPAR gamma2 gene among native Javanese is lower than that in other ethnic groups. No association is seen between the Pro12Ala and diabetes (0.01 vs 0.017%, p = 0.404), a trend of the higher BMI was observed in Pro12Ala carriers in nondiabetic subjects, although this association is limited by small numbers. CONCLUSION: In this study, no association is seen between the Pro12Ala polymorphism in PPAR gamma2 gene and diabetes; a weak association with obesity is seen.
Assuntos
Obesidade/genética , PPAR gama/genética , Polimorfismo Genético/genética , Idoso , Alanina/genética , Alelos , Povo Asiático , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Prolina/genéticaRESUMO
3,3',4,4',5-Pentachlorobiphenyl (PCB126), a congener with a planar configuration, has been established to have relatively strong toxicities similar to those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via aryl hydrocarbon receptors. We investigated the effects of this coplanar PCB on mammalian early spermatogenesis and steroidogenesis in a mouse neonatal testicular organ culture system. Testes collected from newborn mice were subjected to organ culture in medium containing 0, 10, 100 or 1000 nM PCB126. Histochemical analysis revealed that the BrdU-labeling indices of both spermatogenic cells and Sertoli cells were unchanged in all testis specimens exposed to the coplanar PCB. CYP1A1 and steroidogenic enzymes (P450scc, P450c17, 3beta-HSD and 17beta-HSD) mRNA levels were determined by semiquantitative RT-PCR. The CYP1A1 mRNA level in cultured testis was significantly increased by PCB126 in a dose-dependent manner. Although mRNA levels of 3beta-HSD and 17beta-HSD were unchanged, the P450scc mRNA level was significantly down-regulated by PCB126 in a dose-dependent manner. In contrast, the P450c17 mRNA level was significantly higher in 1000 nM PCB126-exposed testis than in control testis. These results suggest that the coplanar PCB does not alter the proliferative activity of spermatogenic cells and Sertoli cells in neonatal testis, but that it directly affects the expression of steroidogenic enzyme genes.
Assuntos
Antagonistas de Estrogênios/toxicidade , Bifenilos Policlorados/toxicidade , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia , Animais , Animais Recém-Nascidos , Divisão Celular , Citocromo P-450 CYP1A1/análise , Citocromo P-450 CYP1A1/biossíntese , Regulação para Baixo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Técnicas de Cultura de Órgãos , RNA Mensageiro/análiseRESUMO
Serotonin (5-HT)1A receptors modulate in vivo release of brain monoaminergic neurotransmitters which may be involved in isolation-induced aggressive behavior. The present study examined the effect of isolation rearing on the 5-HT1A receptor-mediated modulation of dopamine (DA), 5-HT and noradrenaline (NA) release in the frontal cortex of mice. The selective 5-HT1A receptor agonist (S)-5-[-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole HCl (MKC-242) increased the release of DA and NA and decreased the release of 5-HT in the frontal cortex of mice. The effect of MKC-242 on DA release was significantly less in isolation-reared mice than in group-reared mice, while effects of the drug on NA and 5-HT release did not differ between both groups. The effect of the other 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin on cortical DA release was also less in isolation-reared mice than in group-reared mice, and that of the drug on cortical 5-HT release did not differ between both groups. In contrast to MKC-242-induced DA release, amphetamine-induced increase in cortical DA release in vivo was greater in isolation-reared mice. The present findings suggest that isolation rearing enhances the activity of cortical dopaminergic neurons and reduces selectively the 5-HT1A receptor-mediated release of DA in the cortex.
Assuntos
Dopamina/metabolismo , Lobo Frontal/metabolismo , Receptores de Serotonina/metabolismo , Isolamento Social , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Anfetamina/farmacologia , Animais , Dioxanos/farmacologia , Dioxóis/farmacologia , Dopamina/análise , Inibidores da Captação de Dopamina/farmacologia , Lobo Frontal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Microdiálise , Norepinefrina/análise , Norepinefrina/metabolismo , Receptores de Serotonina/efeitos dos fármacos , Receptores 5-HT1 de Serotonina , Serotonina/análise , Serotonina/metabolismo , Agonistas do Receptor de Serotonina/farmacologiaRESUMO
The effect of the benzodiazepine receptor antagonist flumazenil was examined on an antiaggressive effect of (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3- benzodioxole HCl (MKC-242), a 5-HT(1A) receptor agonist. MKC-242 (0.1-1.0 mg/kg, p.o.) selectively reduced isolation-induced aggressive behavior in a dose-dependent manner. Flumazenil (10 mg/kg, i.p.) antagonized the antiaggressive effects of MKC-242 and diazepam, although it alone did not affect the behaviors of isolated mice. These findings suggest that a gamma-aminobutyric acid(A) (GABA(A)) receptor system is involved in the antiaggressive effect by 5-HT(1A) receptor activation.
Assuntos
Agressão/efeitos dos fármacos , Dioxanos/farmacologia , Dioxóis/farmacologia , Receptores de GABA-A/metabolismo , Receptores de Serotonina/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Sítios de Ligação , Diazepam/farmacologia , Relação Dose-Resposta a Droga , Flumazenil/farmacologia , Moduladores GABAérgicos/farmacologia , Masculino , Camundongos , Piperazinas/farmacologia , Piridinas/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Receptores 5-HT1 de Serotonina , Antagonistas da Serotonina/farmacologia , Isolamento SocialRESUMO
Pituitary adenylate cyclase-activating polypeptide (PACAP) has been conserved remarkably during evolution and is widely expressed in the mammalian brain. In Drosophila, mutation of the PACAP homologue results in behavioral defects, including impaired olfaction-associated learning and changes in ethanol sensitivity. Here, we report the generation of mice lacking the PACAP gene (PACAP(-/-)). PACAP(-/-) mice were born in the expected Mendelian ratios but had a high early-mortality rate. The surviving adult PACAP(-/-) mice displayed remarkable behavioral changes; they exhibited hyperactive and explosive jumping behaviors in an open field, increased exploratory behavior, and less anxiety in the elevated plus maze, emergence, and novel-object tests. Analysis of PACAP(-/-) mice brains revealed that the serotonin metabolite 5-hydroxyindoleacetic acid was slightly decreased in the cortex and striatum compared with wild-type mice. The present study provides evidence that PACAP plays a previously uncharacterized role in the regulation of psychomotor behaviors.
Assuntos
Neuropeptídeos/fisiologia , Desempenho Psicomotor , Animais , Sequência de Bases , Encéfalo/metabolismo , Catalepsia/induzido quimicamente , Primers do DNA , Haloperidol/farmacologia , Ácido Hidroxi-Indolacético/metabolismo , Camundongos , Camundongos Knockout , Neuropeptídeos/genética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Desempenho Psicomotor/efeitos dos fármacos , Serotonina/metabolismoRESUMO
OBJECTIVE: The CD36 molecule is expressed in platelets, monocytes, erythroblasts, and other different tissues. The two types of platelet CD36 deficiency, types I and II, are associated with the absence and presence of CD36 on monocytes, respectively. To clarify the involvement of the erythroid lineage in CD36 deficiency, we investigated the phenotype and RNA expression of CD36. MATERIALS AND METHODS: CD36 expression was examined in 296 patients with several cardiovascular diseases in our outpatient clinic. There were 12 patients with type I deficiency and 16 with type II CD36 deficiency. A bone marrow sample was examined in five type I and four type II patients. Expression of CD36 mRNA was examined in burst-forming unit-erythroid (BFU-E). The sequences of reverse transcriptase polymerase chain reaction (RT-PCR) products of the CD36 mRNA from monocytes were examined. RESULTS: As expected, CD36 was deficient in erythroblasts from all five patients with type I deficiency. CD36 was present in erythroblasts from three of the four with type II deficiency, suggesting that their abnormality is restricted to platelets (type IIa). CD36 was unexpectedly absent from erythroblasts of a single type II patient (type IIb). CD36-specific mRNA was identified in BFU-E from each of two normals, six type I, and six type II patients, including type IIb. The sequences of RT-PCR products of the CD36 mRNA in a patient with type IIa and another with type IIb showed homozygous wild alleles. CONCLUSION: The findings provide evidence for further heterogeneity among CD36-deficient individuals and the existence of a basic principle mechanism of type II, such as glycosylation abnormality.
Assuntos
Antígenos CD36/genética , Doenças Cardiovasculares/genética , Hematopoese/imunologia , Monócitos/fisiologia , Angina Pectoris/genética , Antígenos CD/genética , Cardiomiopatia Dilatada/genética , Cardiomiopatia Hipertrófica/genética , Células Cultivadas , Mapeamento Cromossômico , Cromossomos Humanos Par 7 , Ensaio de Unidades Formadoras de Colônias , Éxons , Citometria de Fluxo , Humanos , Imunoglobulina G/sangue , Biossíntese de Proteínas , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) inhibits cell proliferation and is a very effective inducer of apoptosis in a variety of carcinoma cell lines. In order to obtain greater insight into the mechanism of AHPN-induced growth arrest and apoptosis, we began to examine AHPN-induced changes in gene expression by cDNA array screening using human lung carcinoma H460 cells. This analysis identified several AHPN-inducible genes, including the immediate-early genes Egr-1 and Nur77. AHPN was able to increase Egr-1 and Nur77 mRNA expression and protein in a variety of carcinoma cell lines. This induction appeared to be regulated at the transcriptional level and was specific for AHPN since an RAR- and an RXR-selective retinoid were inactive. These results suggest that the induction of Egr-1 and Nur77 by AHPN is independent of nuclear retinoid receptors and involves a novel mechanism. Overexpression of Bcl-2, which inhibits AHPN-induced apoptosis but not growth arrest in human T cell lymphoma Molt-4 cells, did not block the induction of immediate-early gene expression. Treatment of H460 cells with AHPN induced activation of the p38 MAP-kinase but not the ERK1/2 signaling pathway. However, inhibition of the ERK1/2 signaling pathway by PD98059 blocked the induction of Egr-1 and Nur77 mRNA while the p38 MAPK inhibitor PD169316 had little effect. Expression of a dominant-negative ERK1 completely abolished the increase in Egr-1 mRNA. Treatment with MAPK inhibitors or expression of dnERK1 reduced but did not block AHPN-induced apoptosis. Our results suggest that the induction of Egr-1 in H460 by AHPN requires active ERK1/2 and is independent of p38 activation. Egr-1, in cooperation with several other growth-suppressor proteins, is likely involved in AHPN-induced inhibition of cell growth and cell death.
Assuntos
Antineoplásicos/farmacologia , Apoptose , Carcinoma/patologia , Proteínas de Ligação a DNA/biossíntese , Proteínas Imediatamente Precoces , Neoplasias Pulmonares/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Retinoides/farmacologia , Fatores de Transcrição/biossíntese , Carcinoma/genética , Carcinoma/metabolismo , Divisão Celular , Proteínas de Ligação a DNA/genética , Proteína 1 de Resposta de Crescimento Precoce , Ativação Enzimática , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Modelos Biológicos , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , RNA Neoplásico/biossíntese , Fatores de Transcrição/genética , Ativação Transcricional , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
The effect of the newly synthesized compound 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400) on the Na+-Ca2+ exchanger (NCX) was investigated and compared against that of 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea (KB-R7943). In addition, the effects of SEA0400 on reperfusion injury in vitro and in vivo were examined. SEA0400 was extremely more potent than KB-R7943 in inhibiting Na+-dependent Ca2+ uptake in cultured neurons, astrocytes, and microglia: IC50s of SEA0400 and KB-R7943 were 5 to 33 nM and 2 to 4 microM, respectively. SEA0400 at the concentration range that inhibited NCX exhibited negligible affinities for the Ca2+ channels, Na+ channels, K+ channels, norepinephrine transporter, and 14 receptors, and did not affect the activities of the Na+/H+ exchanger, Na+,K+-ATPase, Ca2+-ATPase, and five enzymes. SEA0400, unlike KB-R7943, did not inhibit the store-operated Ca2+ entry in cultured astrocytes. SEA0400 attenuated dose- dependently paradoxical Ca2+ challenge-induced production of reactive oxygen species, DNA ladder formation, and nuclear condensation in cultured astrocytes, whereas it did not affect thapsigargin-induced cell injury. Furthermore, administration of SEA0400 reduced infarct volumes after a transient middle cerebral artery occlusion in rat cerebral cortex and striatum. These results indicate that SEA0400 is the most potent and selective inhibitor of NCX, and suggest that the compound may exert protective effects on postischemic brain damage.
Assuntos
Astrócitos/efeitos dos fármacos , Isquemia Encefálica , Córtex Cerebral/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Traumatismo por Reperfusão , Trocador de Sódio e Cálcio/antagonistas & inibidores , Tioureia/análogos & derivados , Compostos de Anilina/farmacologia , Animais , Animais Recém-Nascidos , Astrócitos/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Córtex Cerebral/patologia , Corpo Estriado/patologia , Canais Iônicos/antagonistas & inibidores , Canais Iônicos/metabolismo , Transporte de Íons/efeitos dos fármacos , Transporte de Íons/fisiologia , Éteres Fenílicos/farmacologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Trocador de Sódio e Cálcio/fisiologia , Tioureia/farmacologiaRESUMO
The atomic force microscope (AFM) is a new useful tool to examine the surface structure of specimens with a higher resolution than the conventional scanning electron microscope. In the present study, we used the AFM to observe the surface of paraformaldehyde-fixed human lymphocytes processed for histochemistry using a biotinylated lectin, wheat germ agglutinin, followed by colloidal gold and silver-enhancement method. Before the treatment, no particles were attached to the cell surface. After treatment, many particles about 100 to 150 nm in diameter were visualized on it. Since we could observe the same cells on the slide glass before and after treatment, the AFM has the advantage to enable us the repeated imaging of samples treated with various kinds of histochemistries.
Assuntos
Linfócitos/ultraestrutura , Microscopia de Força Atômica , Biotinilação , Membrana Celular/química , Histocitoquímica , Humanos , Linfócitos/química , Coloração pela Prata , Propriedades de Superfície , Aglutininas do Germe de Trigo/químicaRESUMO
To assess the health risks associated with exposure to 2,3,7,8-tetrachlorodebenzo-p-dioxin (TCDD), we studied the effects of a relatively low dose of TCDD on the male reproductive system of rats, using the experimental protocol of T. A. Mably et al. (1992, Toxicol. Appl. Pharmacol. 114, 97-107, 108-117, 118-126), and searched for the most sensitive and reliable among several indices of TCDD toxicity. Pregnant Holtzman rats were given a single oral dose of 0, 12.5, 50, 200, or 800 ng TCDD/kg body weight on gestational day (GD) 15, and male offspring were sacrificed on postnatal day (PND) 49 or 120. GC-MS analysis of the abdominal fat tissue and testis clearly showed increased amounts of TCDD in these offspring. However, there was no TCDD effect on body weight of offspring. There were no changes on testicular or epididymal weights by TCDD administration, even at the 800-ng/kg dose in rats sacrificed on either PND 49 or 120. In addition, TCDD administration resulted in no changes in daily sperm production or sperm reserve at any of the doses used. However, the weight of the urogenital complex, including the ventral prostate, was significantly reduced at doses of 200 and 800 ng TCDD/kg in rats sacrificed on PND 120. Moreover, the anogenital distance (AGD) of male rats sacrificed on PND 120 showed a significant decrease in the groups receiving doses greater than 50 ng TCDD/kg. TCDD administration resulted in no apparent dose-dependent changes in levels of either serum testosterone or luteinizing hormone. Interestingly, reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that, in the ventral prostates of the PND 49 group, TCDD administration resulted in both a dose-dependent increase in 5alpha-reductase type 2 (5alphaR-II) mRNA level and a dose-dependent decrease in androgen receptor (AR) mRNA level. These results suggest that low-dose TCDD administration had a greater effect on the development of the external genital organs and ventral prostate than on development of the testis and other internal genital organs. Moreover, it is highly suggested that the decrease in the size of the ventral prostate by maternal TCDD exposure might be due to decreased responsiveness of the prostate to androgen due to an insufficient expression level of androgen receptor during puberty.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Poluentes Ambientais/toxicidade , Dibenzodioxinas Policloradas/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Próstata/efeitos dos fármacos , Próstata/metabolismo , Receptores Androgênicos/metabolismo , Maturidade Sexual/efeitos dos fármacos , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Tecido Adiposo/metabolismo , Animais , Relação Dose-Resposta a Droga , Regulação para Baixo , Poluentes Ambientais/farmacocinética , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Exposição Materna , Dibenzodioxinas Policloradas/farmacocinética , Gravidez , Próstata/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Contagem de Espermatozoides , Testículo/metabolismo , Testículo/patologia , Distribuição TecidualRESUMO
The present study examined the effects of social isolation on cortical dopamine (DA) release in vivo and on brain DA receptor functions to study the possible involvement of cortical DA neurons in an antiaggressive effect of the serotonin (5-HT)1A receptor agonist (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino] propoxy]-1,3-benzodioxole HCl (MKC-242). MKC-242 and the DA receptor agonist apomorphine reduced aggressive behavior in isolated mice. MKC-242 increased cortical DA release in vivo in mice, and the effect was antagonized by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide. The basal level of extracellular DA in the frontal cortex was higher in isolated mice than in grouped mice. MKC-242-induced and high K(+)-induced increases in the cortical DA release were less pronounced in isolated mice than in grouped mice. The effect of apomorphine on locomotor activity was more pronounced in isolated mice than in grouped mice. These findings suggest that the isolation stress enhances cortical DA release and the brain DA receptor function and reduces the responses of the dopaminergic terminals to 5-HT1A receptor stimulation and high K(+)-induced depolarization.
Assuntos
Agressão/fisiologia , Encéfalo/fisiologia , Dopamina/fisiologia , Isolamento Social , Agressão/efeitos dos fármacos , Animais , Apomorfina/farmacologia , Encéfalo/metabolismo , Dioxanos/farmacologia , Dioxóis/farmacologia , Dopamina/metabolismo , Agonistas de Dopamina/farmacologia , Lobo Frontal/efeitos dos fármacos , Masculino , Camundongos , Microdiálise , Atividade Motora/efeitos dos fármacos , Receptores Dopaminérgicos/fisiologia , Agonistas do Receptor de Serotonina/farmacologiaRESUMO
We have studied cyclopiazonic acid (CPA)-sensitive store-operated Ca(2+) entry (SOCE) in cultured neurons and astrocytes and examined the effect of 2-[2-[4-(4-nitrobenzyloxy)phenyl]]isothiourea (KB-R7943), which is often used as a selective inhibitor of the Na(+)-Ca(2+) exchanger (NCX), on the SOCE. CPA increased transiently intracellular Ca(2+) concentration ([Ca(2+)](i)) followed by a sustained increase in [Ca(2+)](i) in neurons and astrocytes. The sustained increase in [Ca(2+)](i) depended on the presence of extracellular Ca(2+) and inhibited by SOCE inhibitors, but not by a Ca(2+) channel inhibitor. CPA also caused quenching of fura-2 fluorescence when the cells were incubated in Mn(2+)-containing medium. KB-R7943 at 10 microM inhibited significantly CPA-induced sustained increase in [Ca(2+)](i) in neurons and astrocytes. KB-R7943 also inhibited CPA-induced quenching of fura-2 fluorescence in the presence of extracellular Mn(2+). These results indicate that cultured neurons and astrocytes possess SOCE and that KB-R7943 inhibits not only NCX but also SOCE.
Assuntos
Astrócitos/metabolismo , Cálcio/metabolismo , Córtex Cerebral/metabolismo , Neurônios/metabolismo , Trocador de Sódio e Cálcio/antagonistas & inibidores , Tioureia/análogos & derivados , Animais , Animais Recém-Nascidos , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Células Cultivadas , Córtex Cerebral/citologia , Cinética , Manganês/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Ratos , Ratos Wistar , Tioureia/farmacologiaRESUMO
We examined the relative amounts of Na(+)-Ca(2+) exchanger (NCX) isoform mRNAs in cultured neurons, astrocytes and developmental rat brain. NCX1 transcript was predominant in neurons and astrocytes, but NCX2 transcript was about four-fold higher than NCX1 or NCX3 transcript in adult rat cortex. NCX2 transcript in the cortex increased markedly during postnatal development, whereas NCX1 and NCX3 transcripts decreased. Na(+)-dependent 45Ca(2+) uptake in the cortical homogenate increased significantly during postnatal development.