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M Taketo

Publications and source records attributed to M Taketo.

At least 19 recordsLinked to original sources
PubMed2004

Calcium-independent inhibition of GABA(A) current by caffeine in hippocampal slices.

Although inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptor is thought to be affected by intracellular calcium ion concentration ([Ca2+]i), origin or route of [Ca2+]i increment has not been well elucidated. Reports on the effect of [Ca2+]i elevation on GABA(A)ergic IPSCs per se are also controversial. In this study, effects of caffeine and several other [Ca2+]i-mobilizing drugs were examined on the IPSCs in acute slices of rat hippocampus. Using the patch clamp recording method, spontaneous and evoked currents were recorded from CA3 neurons. Caffeine strongly inhibited both extra-synaptic and synaptic GABAergic IPSCs, regardless of the presence or absence of extracellular Ca2+. This inhibition was not relieved by the intracellular application of EGTA or 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA). This inhibition by caffeine was not prevented by preequilibration with caffeine. Ca2+ store depletion caused by thapsigargin or repetitive stimulation by caffeine could not prevent the inhibition. Moreover, ruthenium red and ryanodine could not overcome the inhibition. On the contrary, GABA(A)ergic currents were not inhibited by stimulation with several Ca2+-mobilizing agonists. Forskolin could not mimic the effect of caffeine on the IPSC, and caffeine inhibited the IPSC in the presence of adenosine. These results suggest that intracellular Ca2+ mobilization through ryanodine-sensitive store stimulation does not significantly affect GABAergic IPSCs, and most of the inhibitory effect of caffeine is independent of [Ca2+]i elevation under the present experimental conditions.

Acetylcholine↗
PubMed2001

Signal transduction from bradykinin, angiotensin, adrenergic and muscarinic receptors to effector enzymes, including ADP-ribosyl cyclase.

Muscarinic acetylcholine receptors in NG108-15 neuroblastoma x glioma cells, and beta-adrenergic or angiotensin II receptors in cortical astrocytes and/or ventricular myocytes, utilize the direct signaling pathway to ADP-ribosyl cyclase within cell membranes to produce cyclic ADP-ribose (cADPR) from beta-NAD+. This signal cascade is analogous to the previously established transduction pathways from bradykinin receptors to phospholipase Cbeta and beta-adrenoceptors to adenylyl cyclase via G proteins. Upon receptor stimulation, the newly-formed cADPR may coordinately function to upregulate the release of Ca2+ from the type II ryanodine receptors as well as to facilitate Ca2+ influx through voltage-dependent Ca2+ channels. cADPR interacts with FK506, an immunosuppressant, at FKBP12.6, FK506-binding-protein, and calcineurin, or ryanodine receptors. cADPR also functions through activating calcineurin released from A-kinase anchoring protein (AKAP79). Thus, some G(q/11)-coupled receptors can control cADPR-dependent modulation in Ca2+ signaling.

ADP-ribosyl Cyclase↗
PubMed2000

Developmental change of GABA(A) receptor-mediated current in rat hippocampus.

Developmental change of GABA(A)ergic inhibitory postsynaptic current in rat hippocampal CA3 region was examined using patch-clamp recording method. Spontaneous and evoked inhibitory postsynaptic currents were recorded from acute hippocampal slices of neonates (postnatal days 2-4) and adults (days 18-38). Decay kinetics of the spontaneous inhibitory postsynaptic current was slower in neonates than in adults. Application of 500 nM zolpidem increased decay time-constants of the inhibitory postsynaptic currents in both groups with a stronger effect on adults. Zinc (50 microM) inhibited the neonatal inhibitory postsynaptic currents but the inhibition was weaker in adults. Modification of the GABA(A)ergic inhibitory postsynaptic currents by furosemide (0.6 mM) or diazepam (100 nM) did not cause marked differences between the neonate and adult groups. These results demonstrate that GABA(A)ergic inhibitory postsynaptic currents in hippocampal CA3 pyramidal cells change developmentally and indicate that different receptor isoforms are functionally expressed between neonates and adults.

Aging↗
PubMed1999

Structures of mouse Rep-8 cDNA and genomic clones.

A mouse homologue of the human Rep-8 gene was cloned by PCR methods using degenerate oligonucleotide primers corresponding to highly conserved regions between human and mouse genes, and by the Marathon-Ready cDNA amplification method. The full-length mouse Rep-8 contains 1422 nucleotides and codes for a protein of 277 amino acids with a calculated mol. wt. of 31,519. The overall amino acid sequence homology between mouse and human Rep-8 proteins was 73%, and the overall nucleic acid sequence similarity was 65%. The predicted amino acid sequence of mouse Rep-8 has leucine zipper-like motifs in the N-terminal region, similar to the human Rep-8 protein. Rep-8 exists as a single-copy gene and is expressed in both the early and late embryonic stages of mouse development, suggesting that the Rep-8 gene product has an important role in embryogenesis. The genomic structure of the mouse Rep-8 gene was characterized extensively so that a gene targeting strategy could be used to develop an understanding of the biological function(s) of this interesting gene and its product.

Amino Acid Sequence↗
PubMed1999

Potential mechanism for bradykinin-activated and inositol tetrakisphosphate-dependent Ca2+ influx by Ras and GAP1 in fibroblast cells.

Here we propose a molecular model for bradykinin receptor-operated and second messenger (inositol-1,3,4,5-tetrakisphosphate)-evoked Ca2+ influx and its potentiation by oncogenic Ras, which is not store-depletion-induced, so-called capacitative, Ca2+ influx. The principal idea for this hypothesis stems from observation that two bradykinin B2 receptor-activated signal pathways, protein tyrosine phosphorylation and formation of inositol tetrakisphosphate, merge during the Ca2+ influx process and that GTPase activating-protein 1 (GAP 1) is inositol tetrakisphosphate binding protein.

3T3 Cells↗
PubMed1997

Muscarinic receptor-mediated dual regulation of ADP-ribosyl cyclase in NG108-15 neuronal cell membranes.

Cyclic ADP-ribose (cADP-ribose) is an endogenous modulator of ryanodine-sensitive Ca2+ release channels. An unsolved question is whether or not cADP-ribose mediates intracellular signals from hormone or neurotransmitter receptors. The first step in this study was to develop a TLC method to measure ADP-ribosyl cyclase, by which conversion of [3H]NAD+ to [3H]cADP-ribose was confirmed in COS-7 cells overexpressing human CD38. A membrane fraction of NG108-15 neuroblastoma x glioma hybrid cells possessed ADP-ribosyl cyclase activity measured by TLC. Carbamylcholine increased this activity by 2.6-fold in NG108-15 cells overexpressing m1 or m3 muscarinic acetylcholine receptors (mAChRs), but inhibited it by 30-52% in cells expressing m2 and/or m4 mAChRs. Both of these effects were mimicked by GTP. Pretreatment of cells with cholera toxin blocked the activation, whereas pertussis toxin blocked the inhibition. Application of carbamylcholine caused significant decreases in NAD+ concentrations in untreated m1-transformed NG108-15 cells, but an increase in cholera toxin-treated cells. These results suggest that mAChRs couple to ADP-ribosyl cyclase within cell membranes via trimeric G proteins and can thereby control cellular function by regulating cADP-ribose formation.

ADP-ribosyl Cyclase↗
PubMed1997

Inositol-1,3,4,5-tetrakisphosphate binding sites in control and ras-transformed NIH/3T3 fibroblasts.

Inositol-1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) binding properties were investigated in NIH/3T3 fibroblasts and its ras-transformant (DT cells), in which inositol tetrakisphosphates induce Ca2+ influx. [3H]-Ins(1,3,4,5)P4 bound to membranes of both types of cells with Kd values of 10.6 and 8.6 nM, respectively. The rank order of inositol polyphosphates for displacing [3H]Ins(1,3,4,5)P4 in DT cells was Ins(1,3,4,5)P4 > inositol-1,3,4,5,6-pentakisphosphate > inositol hexakisphosphate > inositol-1,4,5-trisphosphate. This order is similar to that reported in two Ras-GTPase-activating proteins, GAP1IP4BP and GAP1m, which are also the Ins(1,3,4,5)P4 binding proteins. Northern blot analysis revealed that NIH/3T3 and DT cells expressed mRNA species that were hybridizable with GAP1m cDNA. These results suggest that parental and ras-transformed NIH/3T3 fibroblasts possess GAP1-like proteins, which may be responsible for triggering inositol tetrakisphosphate-dependent Ca2 influx.

3T3 Cells↗
PubMed1997

Ca2+ release and Ca2+ influx in Chinese hamster ovary cells expressing the cloned mouse B2 bradykinin receptor: tyrosine kinase inhibitor-sensitive and- insensitive processes.

A cDNA encoding a mouse B2 bradykinin (BK) receptor was stably transfected in Chinese hamster ovary (CHO) cells. In two resulting transformants, mouse B2 BK receptor was found to induce a twofold elevation in the inositol-1,4,5-trisphosphate level. In a pertussis toxin-insensitive manner, BK also produced a biphasic increase in the intracellular Ca2+ concentration ([Ca2+]i). The initial elevation in [Ca2+]i was abolished by thapsigargin pretreatment in Ca(2+)-free medium. The second phase was dependent on external Ca2+. The BK/inositol trisphosphate and thapsigargin-sensitive Ca2+ stores required extracellular Ca2+ for refilling. Ca2+ influx induced by BK and thapsigargin was confirmed by Mn2+ entry through Ca2+ influx pathways producing Mn2+ quenching. Genistein, a tyrosine kinase inhibitor, partially decreased the BK-induced [Ca2+]i increase during the sustained phase and the rate of Mn2+ entry. BK had essentially no effect on the intracellular cyclic AMP level. The results suggest that the mouse B2 BK receptor couples to phospholipase C in CHO cells and that its activation results in biphasic [Ca2+]i increases, by mobilization of intracellular Ca2+ and store-depletion-mediated Ca2+ influx, the latter of which is tyrosine phosphorylation dependent.

Animals↗
PubMed1996

Inositol trisphosphate/Ca2+ as messengers of bradykinin B2 and muscarinic acetylcholine m1-m4 receptors in neuroblastoma-derived hybrid cells.

Neuroblastoma x glioma hybrid NG 108-15 and neuroblastoma x fibroblast hybrid NL308 cells possess endogenous bradykinin B2 receptors and m4 muscarinic acetylcholine receptors (mAChRs), which couple to phospholipase C and adenylate cyclase, respectively. Four genetic subtypes of mAChRs differed in their effects when stimulated in NG108-15 and NL308 cells overexpressing mAChRs. Broadly speaking, the principal effects fell into two categories: the odd-numbered receptors (m1 and m3) activated phospholipase C and increased inositol trisphosphate/Ca2+, as bradykinin did, whereas the even-numbered receptors (m2 and m4) inhibited adenylate cyclase via a pertussis toxin (PTx)-sensitive G-protein in NG108-15 cells. But all four types of NL308 cells overexpressing each m1, m2, m3 and m4 receptor activated phospholipase C, while keeping the PTx-sensitivity in m2/m4, but not in m1/m3 receptors. Coupling to ion channel effectors showed a comparable dichotomy in NG108-15 cells, while cross-activation occurred in NL308 cells.

Animals↗
PubMed1995

Cloning, structural analysis and mapping of the mouse selenocysteine tRNA([Ser]Sec) gene (Trsp).

The tRNA([Ser]Sec) molecule mediates the synthesis of selenoproteins by incorporating selenocysteine into specific UGA codons upon translation of mRNAs that encode selenocysteine-containing proteins. The mouse gene encoding tRNA([Ser]Sec) (Trsp) was isolated from a genomic library and sequenced. The mouse sequence is colinear with its tRNA product, and contains a C to T transition relative to the homologous genes in other vertebrates except rat. Transcriptional control motifs found 5' to the tRNA coding region included a TATA element, a PSE element and an SPH motif which is associated with an octamer motif. A Northern hybridization analysis showed highest expression in the testis, followed by thymus, spleen, kidney, ovary, brain, liver, heart and skeletal muscle. Surprisingly, the expression level was lowest in embryonic stem cells. These results suggest a tissue-specific transcriptional control. Using restriction fragment length variants (RFLVs) in interspecific backcross mice between Mus musculus (C3H strain) and Mus spretus, the Trsp gene was mapped to the proximal region of mouse Chr 7, cosegregating with octamer-binding transcription factor-2 (Otf2).

Amino Acid Sequence↗
PubMed1995

Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene.

Mutations in the APC (adenomatous polyposis coli) gene appear to be responsible for not only familial adenomatous polyposis but also many sporadic cases of gastrointestinal cancers. Using homologous recombination in mouse embryonic stem cells, we constructed mice that contained a mutant gene encoding a product truncated at a 716 (Apc delta 716). Mendelian transmission of the gene caused most homozygous mice to die in utero before day 8 of gestation. The heterozygotes developed multiple polyps throughout the intestinal tract, mostly in the small intestine. The earliest polyps arose multifocally during the third week after birth, and new polyps continued to appear thereafter. Surprisingly, every nascent polyp consisted of a microadenoma covered with a layer of the normal villous epithelium. These microadenomas originated from single crypts by forming abnormal outpockets into the inner (lacteal) side of the neighboring villi. We carefully dissected such microadenomas from nascent polyps by peeling off the normal epithelium and determined their genotype by PCR: all microadenomas had already lost the wild-type Apc allele, whereas the mutant allele remained unchanged. These results indicate that loss of heterozygosity followed by formation of intravillous microadenomas is responsible for polyposis in Apc delta 716 intestinal mucosa. It is therefore unlikely that the truncated product interacts directly with the wild-type protein and causes the microadenomas by a dominant negative mechanism.

Adenoma↗
PubMed1995

Mouse Elk oncogene maps to chromosome X and a novel Elk oncogene (Elk3) maps to chromosome 10.

The Elk protein is a member of the Ets family found in both vertebrates and invertebrates. Human ELK1 encoded by ELK1 binds alone or together with serum response factor to DNA and regulates gene expression in a variety of biological processes. Using a panel of interspecific backcross mice, we have mapped the Elk oncogene (Elk) and a novel type Elk oncogene (Elk3), closely related to ELK1. Elk maps to Chr X, and Elk3 maps to the proximal region of Chr 10.

Animals↗