Search PubMed⌕ Search

Biomedical subjects

K Takuma

Publications and source records attributed to K Takuma.

48 records · Page 3Linked to original sources
PubMed1995

Nitroprusside and cyclic GMP stimulate Na(+)-Ca2+ exchange activity in neuronal preparations and cultured rat astrocytes.

The effects of nitric oxide (NO)-generating agents on 45Ca2+ uptake in rat brain slices and cultured rat astrocytes were studied in the presence of monensin, which is considered to drive the Na(+)-Ca2+ exchanger in the reverse mode. Sodium nitroprusside (SNP) at > 10 microM increased monensin-stimulated Ca2+ uptake in the slices, although it did not affect high K(-)-stimulated Ca2+ uptake. Another NO donor, 3-morpholinosydnonimine, was effective. The effect of SNP was antagonized by hemoglobin (50 microM), a NO scavenger, and mimicked by 8-bromo-cyclic GMP (100 microM). In rat brain synaptosomes, SNP increased monensin-stimulated Ca2+ uptake, but it did not affect high K(+)-stimulated Ca2+ uptake. 8-Bromocyclic GMP, but not SNP, increased Na(+)-dependent Ca2+ uptake significantly in synaptic membrane vesicles in the absence of monensin. In cultured rat astrocytes, SNP and 8-bromo-cyclic GMP increased Ca2+ uptake in the presence of ouabain and monensin, which were required for the Ca2+ uptake in the cells. These findings suggest that NO stimulates the Na(+)-Ca2+ exchanger in neuronal preparations and astrocytes in a cyclic GMP-dependent mechanism.

Animals↗
PubMed1995

Increase of noradrenaline release in the hypothalamus of freely moving rat by postsynaptic 5-hydroxytryptamine1A receptor activation.

1. 5-Hydroxytryptamine (5-HT) plays a role in the regulation of noradrenergic neurones in the brain, but the precise mechanism of regulation of noradrenaline (NA) release by 5-HT1A receptors has not been defined. The present study describes the effect of a highly potent and selective 5-HT1A receptor agonist, 5-(3-[[(2S)-1,4-benzodioxan-2-ylmethyl)]amino]propoxy)-1,3-b enzodioxole HC1 (MKC-242), on NA release in the hypothalamus using microdialysis in the freely moving rat. 2. Subcutaneous injection of MKC-242 (0.5 mg kg-1) increased extracellular levels of NA and its metabolite, 3-methoxy-4-hydroxyphenylglycol, in the hypothalamus and hippocampus. 3. The 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.2 mg kg-1) and buspirone (3 mg kg-1) mimicked the effect of MKC-242 in increasing NA release in the hypothalamus. 4. The effects of MKC-242 and 8-OH-DPAT in the hypothalamus were antagonized by pretreatment with WAY100135 (10 mg kg-1), a silent 5-HT1A receptor antagonist. 5. Local administration of 8-OH-DPAT (10-100 microM), citalopram (1 microM), a 5-HT reuptake inhibitor, and MDL72222 (10 microM), a 5-HT3 receptor antagonist, into the hypothalamus, had no effect on NA release. 6. Intracerebroventricular injection with 5,7-dihydroxytryptamine caused a marked reduction in brain 5-HT content, but the treatment affected neither basal NA levels nor the MKC-242-induced increase in NA release. 7. The effect of MKC-242 in increasing NA release was not attenuated by repeated treatment with the drug (0.5 mg kg-1, once a day for 2 weeks). 8. The present results suggest that activation of postsynaptic 5-HT1A receptors increases NA release in the hypothalamus.

5,7-Dihydroxytryptamine↗
PubMed1995

Effects of serotonin1A agonists on anoxia-induced impairment of protein synthesis in rat brain slices.

Earlier in vivo experiments suggest that serotonin1A (5-HT1A) agonists are new tools for the treatment of experimental cerebral ischemia. The present study examined this idea in an in vitro system. Incubation of rat brain slices under anoxic conditions for 30 min decreased protein synthesis that was assayed in a normoxic medium by measuring the incorporation of [14C]lysine into trichloroacetic acid-insoluble tissue extracts. The 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino) tetralin (10-100 microM) and buspirone (50 microM) attenuated the anoxia-induced decrease in protein synthesis in the slices. Although the degree of the effect is small, it may be relevant to the neuroprotective effect in the in vivo experiments.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Novel benzodioxan derivative, 5-(3-[((2S)-1,4-benzodioxan-2- ylmethyl)amino]propoxy)-1,3-benzodioxole HCl (MKC-242), with a highly potent and selective agonist activity at rat central serotonin1A receptors.

The present study characterizes the neurochemical profile of the newly synthesized compound 5-(3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy)-1,3-be nzodioxole HCl (MKC-242). In in vitro experiments, MKC-242 had high affinity for serotonin1A (5-HT1A) receptors (Ki: 0.35 nM) and moderate affinity for alpha 1-adrenoceptors (Ki: 21 nM), whereas it had no appreciable affinity for any other neurotransmitter recognition sites studied and 5-HT transporter. MKC-242 (0.3-3.0 mg/kg, s.c.; 1-10 mg/kg, p.o.) caused presynaptic 5-HT1A-receptor-mediated responses (decreases in 5-HT turnover and 5-HT release) and postsynaptic 5-HT1A-receptor-mediated responses (hypothermia, an increase in serum corticosterone level and 5-HT1A behavioral syndrome). The effects of MKC-242 on decarboxylase inhibitor-induced 5-hydroxytryptophan accumulation and rectal temperature were blocked by the 5-HT1A-receptor antagonist N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropana mide. The comparative studies on the in vivo responses induced by MKC-242 and the 5-HT1A-receptor full agonist 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) showed that MKC-242 and 8-OH-DPAT had similar efficacy at presynaptic 5-HT1A receptors, whereas the former had less efficacy than the latter at postsynaptic 5-HT1A receptors. Furthermore, MKC-242 partially inhibited forskolin-stimulated adenylate cyclase activity in hippocampal membranes. These findings suggest that MKC-242 acts as a full and partial agonist at pre- and postsynaptic 5-HT1A receptors, respectively, in the central nervous system.

5-Hydroxytryptophan↗
PubMed1994

Corticotropin-releasing factor stimulates Ca2+ influx in cultured rat astrocytes.

Corticotropin-releasing factor (CRF) increased intracellular Ca2+ concentration in single astrocytes. The effect in increasing intracellular Ca2+ was not observed in Ca2(+)-free solution. Furthermore, CRF at concentrations more than 10 nM stimulated 45Ca2+ uptake in cultured rat astrocytes. The action was blocked by alpha-helical CRF(9-41) in a competitive manner, but not by nifedipine and 3,4-dichlorobenzamil. On the other hand, CRF did not stimulate cAMP formation, cGMP formation and phosphoinositide hydrolysis in astrocytes. These results indicate that CRF increases Ca2+ influx via an activation of CRF receptors in a cAMP-independent mechanism in cultured astrocytes.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Cultured rat astrocytes possess Na(+)-Ca2+ exchanger.

Na(+)-Ca2+ exchange activity in its reverse mode was demonstrated in cultured rat astrocytes. Combination of ouabain (1 mM) and monensin (20 microM) caused a marked increase in 45Ca2+ uptake in astrocytes. 45Ca2+ uptake was also stimulated by lowering the external Na+ concentration. Ouabain plus monensin-stimulated 45Ca2+ uptake was blocked by 3,4-dichlorobenzamil (IC50, 16 microM), an inhibitor of Na(+)-Ca2+ exchanger, but not by nifedipine (0.1 microM). The stimulated-45Ca2+ uptake was observed even in K(+)-free medium, and external K+ at 5-10 mM caused a 2.2-fold increase in the uptake. Microspectrofluorimetry using the Ca(2+)-sensitive dye fura-2 showed that ouabain plus monensin increased intracellular Ca2+ concentration in single astrocytes. The Ca2+ signal was dependent on external Ca2+ (EC50, 1.4 mM), and blocked by 20 microM 3,4-dichlorobenzamil, but not by Ca2+ channel blockers (Cd2+, 20 microM; Ni2+, 100 microM). Antiserum of cardiac Na(+)-Ca2+ exchanger recognized 160 and 120-135 kDa proteins on SDS-polyacrylamide gel electrophoresis of astrocyte homogenate. Northern blot analysis revealed the presence of mRNA for the exchanger protein in astrocytes. These findings indicate that Na(+)-Ca2+ exchanger which is modulated by K+ is present in cultured rat astrocytes.

Amiloride↗
PubMed1994

Colorectal carcinoma metastatic to skeletal muscle.

Skeletal muscle is one of the most unusual sites of metastasis from any malignancy. We report on a case of skeletal muscle metastasis from colonic carcinoma, and review seven previously reported cases. The patient was a 66-year-old man who exhibited a painful metastatic mass in the right major teres muscle six months after surgery for colonic carcinoma. He underwent three operations and one course of arterial infusion chemotherapy, but died of carcinoma after two years and seven months. In seven previous cases and in the present case (3 males and 5 females, aged between 30 and 75 years), the sites of the primary lesion and metastatic lesion in skeletal muscle were diverse. The interval between primary carcinoma and relapse ranged from synchronous to 5 years. Spontaneous pain in the recurrent region was a characteristic symptom. Surgical removal of the metastatic lesions relieved pain. Prognosis was considered poor. However, complete resection of the metastatic lesion at a time when no other recurrent lesions were present might have cured the patient.

Adenocarcinoma↗
PubMed1994

[Intractable bacterial infections in surgical patients].

Although many new antibiotics became available for clinical use, intractable bacterial infections are still major cause of morbidity and mortality in surgical patients. The infections are attributable to multiple factors. Surgical stress such as extensive burns and major surgery results in the depressed host-defense function, which is mediated by cytokine responses. Necrotic tissue, ischemia, hematoma, cholelithiasis, foreign bodies, indwelling catheters, intra-tracheal tubes, and other medical devices are local factors making infection resistant to ordinary chemotherapy. Multi-resistant bacteria such as methicillin resistant Staphylococcus aureus and Pseudomonas, and ampicillin resistant enterococci are the main bacteria causing the infections. 32% of surgical specimens isolated two or more bacteria, making the chemotherapy difficult in clinical setting. Importance of surgical drainage, removal of necrosis and the devices are emphasized.

Aged↗
PubMed1993

Selective induction of alpha 1 isoform of (Na+ + K+)-ATPase by insulin/insulin-like growth factor-I in cultured rat astrocytes.

Treatment of cultured rat astrocytes with insulin increased (Na+ + K+)-ATPase activity expressed per protein or DNA by 1.6- to 2.1-fold, but did not affect Mg(2+)-ATPase and adenylate cyclase activities. Insulin treatment increased protein and DNA contents under the conditions, while it did not cause morphological differentiation as determined by a microscopic inspection. Insulin-like growth factor-I (IGF-I) had a similar effect on the enzyme activity in astrocytes: the effect of insulin was observed at supraphysiological concentrations, while that of IGF-I was observed at physiological concentrations. Insulin and IGF-I both stimulated DNA synthesis at the concentrations that caused an increase in enzyme activity. The effect was blocked by tyrosine kinase inhibitors such as genistein and herbimycin A and by cycloheximide. Western blot analysis showed that alpha 1 and alpha 2 isoforms of (Na+ + K+)-ATPase were present in cultured astrocytes and that insulin and IGF-I increased the content of the alpha 1 isoform but did not that of the alpha 2 isoform. Two components of ouabain inhibition were observed in the enzyme purified partially from cultured astrocytes, and treatment of the cells with IGF-I increased the ratio of the low-affinity component of the inhibition, indicating a selective increase in the activity of the alpha 1 isoform. These results indicate that insulin increases (Na+ + K+)-ATPase activity through an activation of IGF-I receptors and the increase is due to the selective induction of the alpha 1 isoform in cultured astrocytes.

Adenylyl Cyclases↗
PubMed1992

Sex difference for tolerance of 5-HT1A receptor-mediated temperature and corticosterone responses in mice.

Repeated treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) resulted in significant attenuation of 8-OH-DPAT-induced hypothermia and adrenocorticol effect in mice of both sexes, while it did not affect the 8-OH-DPAT-induced decrease in 5-hydroxyindoleacetic acid in the hypothalamus in either sex. The attenuated responses developed more rapidly in female than in male mice, indicating sex differences in the adaptive regulation of the 5-HT1A receptor-mediated responses.

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