Biomedical subjects

Sotaro Momosaki

Publications and source records attributed to Sotaro Momosaki.

7 recordsLinked to original sources

PubMed2006

The apparent positive cooperativity of in vivo [3H]PK-11195 binding in mouse fibrosarcoma.

To evaluate the binding properties of peripheral benzodiazepine receptor (PBR) in mouse fibrosarcoma, [(3)H]PK-11195 binding, in vitro and in vivo, was investigated using either tissue dissection or autoradiographic method. The binding characteristics in fibrosarcoma were compared with those in the kidney. The results of an in vitro saturation study revealed that the maximal numbers of PBR binding sites (B(max)) in fibrosarcoma and in the kidney were almost the same (kidney: 5.2 pmol/mg protein; fibrosarcoma: 5.0 pmol/mg protein). On the other hand, the binding affinity (K(d)) in fibrosarcoma was lower than that in the kidney (kidney: 0.45 nM; fibrosarcoma: 1.34 nM). It is noteworthy that the in vivo binding of [(3)H]PK-11195 in fibrosarcoma increased with increasing doses of [(3)H]PK-11195 (in the dose range of 0.03-1 mg/kg), whereas that in the kidney decreased with competitive inhibition. The apparent positive cooperativity of [(3)H]PK-11195 binding in fibrosarcoma was only observed under in vivo conditions and might be possibly related to the incoordination of PBR subunits.

Animals↗

PubMed2006

Evaluation of [14C]phenylacetate as a prototype tracer for the measurement of glial metabolism in the rat brain.

[(14)C]Phenylacetate was designed as a prototype tracer for the measurement of glial metabolism, and its potency in comparison with that of [(14)C]acetate was evaluated in this study. Normal rats were intravenously injected with [(14)C]phenylacetate or [(14)C]acetate, and radioactivity concentrations were measured in the plasma, cerebral cortex, cerebellum and peripheral tissues by dissection method. In addition, [(14)C]phenylacetate uptake in the rat brain was compared by autoradiography with that of [(14)C]acetate following the injection of fluorocitrate, a selective glial toxin, into the brain. [(14)C]Phenylacetate was rapidly taken up into the brain and was retained at high levels up to 20 min postadministration. The levels of [(14)C]phenylacetate in the cerebral cortex were about threefold higher than those of [(14)C]acetate at 1 min postinjection. Microinjection of fluorocitrate into the right striatum resulted in a significant decrease of the uptake of both [(14)C]phenylacetate and [(14)C]acetate into the right striatum. Radiochemical analysis confirmed the rapid hydrolysis of [(14)C]phenylacetate in the rat brain, with less than 20% of radioactivity representing unmetabolized [(14)C]phenylacetate at 1 min postinjection. These results suggest that [(14)C]phenylacetate is rapidly taken up into the brain and is hydrolyzed and converted to [(14)C]acetate. [(14)C]Phenylacetate may have the potential to serve as a tracer for the measurement of glial metabolism in an intact brain.

Acetates↗

PubMed2004

Rat-PET study without anesthesia: anesthetics modify the dopamine D1 receptor binding in rat brain.

Positron emission tomography (PET) measurements in 6-month-old F344/N rats were performed in the conscious state and the influence of chloral hydrate, ketamine, and pentobarbital anesthesia on dopamine D(1) (DA-D(1)) receptor binding was evaluated using [(11)C]SCH23390, a selective DA-D(1) receptor ligand. To perform the PET study in conscious rats, an original fixation apparatus was developed and the animals were trained to acclimate to the scanning atmosphere for 3 h. This training was carried out twice a day for 2 weeks. PET measurements in conscious rats were successful, since the trained rats scarcely moved during the scanning (as monitored by video camera) and since highly reproducible measurements of binding potential (BP) were derived from their scanning. Chloral hydrate and ketamine anesthesia significantly increased the striatal BP of DA-D(1) receptors by 36% and 46%, respectively, compared to that observed in the conscious state. In contrast, pentobarbital markedly decreased the BP by 41%. These BP values of DA-D(1) receptors were calculated using a curve-fitting method. Our results indicate that PET studies in rats should be performed in the conscious state since the anesthetics dramatically modified ligand-receptor bindings, such as DA-D(1) receptor binding, in rat brain.

Anesthesia↗

PubMed2003

Ionic interaction of [11C]-N,alpha-dimethylbenzylamine (DMBA) in rodent brain.

The [S] enantiomer of [11C]-N,alpha-dimethylbenzylamine (DMBA) was synthesized by N-methylation of [S]-alpha-methylbenzylamine, and its biodistribution in mice was measured. [11C]-[S]-DMBA was rapidly distributed into the brain, heart and lungs, and considerable long-term retention in the brain was observed. The radioactive metabolites in the plasma were analyzed by liquid chromatography. Kinetic analysis using unmetabolized [11C]DMBA in the plasma as the input function was performed employing a simplified two-compartment model. The estimated distribution volumes (DV) of [11C]DMBA in the brain and heart were 6.05 and 3.95, respectively. The right striatum of the rat brain was lesioned with ibotenic acid 2 weeks before the tracer experiment. Both in vitro and in vivo autoragiographic studies were performed, and revealed significant reduction of the radioactivity levels in the lesioned striatum. On the other hand, the regional cerebral blood flow, as measured by [14C]iodoantipyrine, was not significantly altered in the lesioned striatum. These results indicate that the ionic binding component for DMBA exists mainly in neural cells rather than in glial cells. [11C]DMBA might be a useful radiotracer for detection of neural cell loss in the brain.

9,10-Dimethyl-1,2-benzanthracene↗

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

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↗