Biomedical subjects

Rie Hosoi

Publications and source records attributed to Rie Hosoi.

7 recordsLinked to original sources

PubMed2003

Sensitivities of benzodiazepine receptor binding and muscarinic acetylcholine receptor binding for the detection of neural cell death caused by sodium nitroprusside microinjection in rat brain.

Sodium nitroprusside (SNP) was microinjected into rat cerebral cortex and changes in muscarinic acetylcholine receptor (mAChR) binding and benzodiazepine receptor (BZR) binding were followed for 24 h after the infusion using [(3)H]-N-methyl-4-piperidyl benzilate ([(3)H]-NMPB) and [(3)H]-flumazenil, respectively, as a radioligand. The microinjection of SNP dose-dependently caused significant neural cell death 3 h after infusion, with the area of cell death becoming extensive 24 h after infusion. Neither SIN-1 nor NOC-18, other types of NO donors, caused neural cell death. Together with the result that deferoxamine, an iron-chelating agent, protected SNP-induced brain injury indicated important roles of iron-related radicals in SNP cytotoxicity in rat brain. In vitro [(3)H]-NMPB binding was significantly reduced in parallel with the time course of neural cell death detected by TTC staining and Nissl staining. In contrast, [(3)H]-flumazenil binding was essentially unaltered during the 24-h period after the SNP infusion. Similar results were observed in in vivo binding experiments. In vivo [(3)H]-NMPB binding was found to be much more sensitive at detecting cell death caused by SNP. On the other hand, [(3)H]-flumazenil binding in vivo was relatively insensitive to SNP-induced cell death. These results indicate that mAChR binding may be superior to BZR binding for detecting cell death in brain tissue, in contrast to what was previously thought.

Animals↗

PubMed2003

Intrastriatal microinjection of sodium nitroprusside induces cell death and reduces binding of dopaminergic receptors.

Rat striatum was microinjected with 50 nmol sodium nitroprusside (SNP) and neural cell death as well as the binding of dopaminergic receptors were followed for 24 h after the infusion using TTC staining, cresyl violet staining, and quantitative autoradiography. Striatal cell death was observed 3 h after the infusion of SNP. A widespread area of cell death, including part of the cerebral cortex, was seen at 24 h after the infusion. A decrease of more than 80% in dopamine D1 receptor binding was seen in rat brain slices prepared 2 h after the infusion of SNP, whereas only a slight decrease in dopamine D2 receptor binding and almost no changes in dopamine transporter binding were observed. One day after the infusion, less than 10% of the binding of all three types of dopaminergic receptors remained in a widespread area in the infused side of the striatum and part of the cerebral cortex. Microinjection of either NOC-18 (50 nmol), another type of NO donor, or sodium cyanide (50 nmol) did not caused cell death. In addition, microinjection of FeCl2 (50 nmol) into the striatum caused cell death and reduction in dopamine D() receptor binding. These results suggest that iron-related radical reactions, but not NO itself, might have important roles on SNP-caused cell death. The current receptor binding study also indicated that dopamine D1 receptor binding is the most sensitive indicator for detection of cell death or cell damage induced by radical reactions in the rat striatum.

Animals↗

PubMed2003

Effect of sabcomeline on muscarinic and dopamine receptor binding in intact mouse brain.

Sabcomeline [(R-(Z)-(+)-alpha-(methoxyiamino)-1-azabicyclo[2.2.2]octane-3-acetonitrile)] is a potent and functionally selective muscarinic M1 receptor partial agonist. However, little is known of the binding properties of sabcomeline under in vivo conditions. In this study, muscarinic receptor occupancy by sabcomeline in mouse brain regions and heart was estimated using [3H]quinuclidinyl benzilate (QNB) and [3H]N-methylpiperidyl benzilate (NMPB) as radioligands. In the cerebral cortex, hippocampus, and striatum, the estimated IC50 value of sabcomeline for [3H]NMPB binding was almost 0.2 mg/kg. Sabcomeline was not a selective ligand to M1 receptors as compared with biperiden in vivo. In the cerebral cortex, maximum receptor occupancy was observed about 1 hr after intravenous injection of sabcomeline (0.3 mg/kg), and the binding availability of mACh receptors had almost returned to the control level by 3-4 hr. These findings indicated that the binding kinetics of sabcomeline is rather rapid in mouse brain. Examination of dopamine D2 receptor binding revealed that sabcomeline affected the kinetics of both [3H]raclopride and [3H]N-methylspiperone (NMSP) binding in the striatum. It significantly decreased the k3 and k4 of [3H]raclopride binding resulting in an increase in binding potential (BP = k3/k4 = Bmax/Kd) in sabcomeline-treated mice, and an approximately 15% decrease in k3 of [3H]NMSP binding was also observed. Although the mechanism is still unclear, sabcomeline altered dopamine D2 receptor affinity or availability by modulations via neural networks.

Animals↗

PubMed2002

Increment of in vivo binding of [3H]SCH 23390, a dopamine D1 receptor ligand, induced by cyclic AMP-dependent protein kinase in rat brain.

The effects of cyclic AMP (cAMP)-related compounds on in vivo [(3)H]SCH 23390 binding to striatal dopamine D(1) receptors were investigated using autoradiography in order to clarify the possible regulation of the cAMP-dependent mechanisms in the in vivo ligand-receptor bindings in the living brain. Intrastriatal infusion of the cAMP analogue, N6,2'-O-dibutyryl-cyclic AMP (db-cAMP; 5, 25 and 100 nmol/side) produced a dose-dependent increase of in vivo [(3)H]SCH 23390 binding in conscious rats. This increasing effect of [(3)H]SCH 23390 binding completely disappeared by 6 h after the infusion of db-cAMP. A similar increase of in vivo [(3)H]SCH 23390 binding to striatal D(1) receptors was also observed by intrastriatal injection of 8-bromo-cyclic AMP (8Br-cAMP, 100 nmol/side). Pretreatment with Rp-cyclic AMP triethylamine (Rp-cAMPS, 100 nmol/side), an inhibitor of the cAMP-dependent protein kinase (PKA), completely blocked the increasing effect of [(3)H]SCH 23390 binding induced by db-cAMP. In contrast, in vitro [(3)H]SCH 23390 binding was not significantly altered by intrastriatal infusion of db-cAMP, which indicated that the maximum number of binding sites (B(max)) for D(1) receptors was not changed. The kinetic analysis employed the graphical method indicated that a db-cAMP-induced increase of in vivo [(3)H]SCH 23390 binding was mainly due to an increase in the bimolecular association rate constant (k(on)). These results strongly indicate that the PKA-mediated phosphorylation may play a pivotal role in the regulating the in vivo [(3)H]SCH 23390 dopamine D(1) receptor binding in intact rat brain.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2002

Rolipram depresses [(3)H]2-deoxyglucose uptake in mouse brain and heart in vivo.

The effects of systemic administration of rolipram, a selective phosphodiesterase type 4 inhibitor, on [(3)H]2-deoxyglucose (DG) uptake in brain and peripheral tissues were examined. Rolipram significantly and dose-dependently decreased [(3)H]DG uptake in brain, heart and skeletal muscle. In contrast, the radioactivity concentrations in the plasma of rolipram-treated mice were significantly higher than those of control mice at all times after injection of the tracer. In the kinetic study, the initial uptake of [(3)H]DG in brain was decreased by rolipram, whereas no significant differences were observed in the uptake in heart and skeletal muscle. However, radioactivity concentrations in the brain, heart and skeletal muscle 30 min after the injection of [(3)H]DG were significantly lowered by rolipram to about 60%, 10% and 10% of control values, respectively. The uptake of [(13)N]ammonia in brain and heart of rolipram-treated mice was slightly decreased, which indicated that rolipram diminished both cerebral and cardiac blood flow. These results indicate that the phosphorylation process via hexokinase rather than the transport of [(3)H]DG might be depressed by rolipram. Together with the previous observations that inhibition of protein kinase A (PKA) markedly enhanced [(14)C]DG uptake in rat brain, these results indicate an important role of the cAMP/PKA systems in the regulation of glucose metabolism in the living brain as well as in peripheral tissues such as the heart and skeletal muscle.

Animals↗

PubMed2002

Enhancement of the relative uptake of 18F-FDG in mouse fibrosarcoma by rolipram.

The effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumor tissue was examined in mice transplanted with NFSa fibrosarcoma. The uptake indexes of 18F-FDG in the heart, skeletal muscle and brain remarkably decreased after treatment with 3 mg/kg of rolipram (heart: 13%, skeletal muscle: 14%, brain: 31%), but fibrosarcoma tissue showed only a 50% reduction in the uptake index of 18F-FDG. The tumor/muscle ratio of radioactivity 30 min after 18F-FDG injection was consequently enhanced from 1.9 to 6.5 by rolipram. This indicates the possible use of rolipram to enhance the sensitivity of tumor detection, as well as characterization of tumors in 18F-FDG PET.

Animals↗

PubMed2002

Changes in histological construction and decrease in 3H-QNB binding in the rat brain after prenatal X-irradiation.

To elucidate the mechanisms involved in deleterious neuronal and behavioral changes after prenatal ionizing irradiation, in vitro muscarinic acetylcholine (mACh) receptor binding and histological construction were investigated in 9-week old rat brains after 1.5 Gy X-ray exposure on embryonic day 15 (E15). A gross anatomical examination with a magnetic-resonance imaging system showed an irregular tissue construction in the hippocampus and cortex of the irradiated rat brain. Histological sections stained with hematoxylin and eosin also indicated that the structures of the hippocampus and cortex were obviously changed. In irradiated rats, the laminar structure of pyramidal cells was selectively deranged in the CA1 region. In vitro 3H-Quinuclidinyl benzilate binding in the hippocampus was significantly decreased (about 10%) in prenatal irradiated rats compared to that in sham-treated rats. On the other hand, no significant change in mACh receptor binding was observed in the cerebral cortex. The present study revealed that prenatal exposure to ionizing radiation may induce dysfunction of the cholinergic neuronal systems, especially in the hippocampus, resulting in deleterious changes in memory and behavior.

Animals↗