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C Tanaka

Publications and source records attributed to C Tanaka.

At least 163 records · Page 9Linked to original sources
PubMed1994

High-affinity specific [3H]tamsulosin binding to alpha 1-adrenoceptors in human prostates with benign prostatic hypertrophy.

The binding of a novel radioligand, [3H]tamsulosin, to human prostatic membranes with benign prostatic hypertrophy (BPH) has been characterized. [3H]Tamsulosin rapidly associated with its binding sites in human prostatic membranes with BPH, and the binding reached steady state by 30 min at 25 degrees C. The rate constants for association and dissociation of [3H]tamsulosin binding were calculated to be 0.21 +/- 0.05/nM per minute and 0.01 +/- 0.004/min, respectively. The specific binding of [3H]tamsulosin in human prostatic membranes was saturable and of high affinity (Kd = 0.04 +/- 0.01 nM). The density of [3H]tamsulosin-binding sites (Bmax) was 409 +/- 28 fmol/mg protein. The Kd and Bmax values for [3H]tamsulosin binding in human prostates were significantly lower than those for [3H]prazosin binding. [3H]tamsulosin binding was remarkable for its significantly lower degree of nonspecific binding. Six alpha-adrenoceptor antagonists competed with [3H]tamsulosin for the binding sites in the rank order: tamsulosin > WB4101 > prazosin > S-(+)-isomer > naftopidil > yohimbine. The binding affinities (pKi) of these antagonists for [3H]tamsulosin binding in human prostates closely correlated with their pharmacological potencies (pA2) in prostates. In conclusion, [3H]tamsulosin selectively labels alpha 1-adrenoceptors in human prostates, and thus may become a useful radioligand for the further analysis of these receptors.

Adrenergic alpha-Antagonists↗
PubMed1994

Alpha 1-adrenoceptors in human prostate: characterization and binding characteristics of alpha 1-antagonists.

The role of alpha 1-adrenoceptors in the mediation of autonomic functions, particularly in the control of the cardiovascular system, is widely known. It has been shown that alpha 1-adrenoceptors localized in human prostate mediate the contraction of prostatic smooth muscles which produces an increase in the intraurethral pressure and thus, these receptors are important in the regulation of bladder outlet resistance. Alpha 1-antagonists such as prazosin relieve the symptoms of bladder outlet obstruction in men with symptomatic benign prostatic hypertrophy (BPH) by blocking alpha 1-adrenoceptors, thereby decreasing prostatic tone and urethral resistance. Thus, alpha 1-adrenergic stimulation may be one of the most important factors in the development of urinary obstruction in BPH. Alpha 1-adrenoceptors in human prostate have been identified and characterized extensively by functional, radioligand binding and molecular biological techniques. These studies provide evidence in support of the concept that the alpha 1C-subtype forms the majority of alpha 1-adrenoceptors in human prostatic smooth muscles. It has been shown that YM617 (tamsulosin) and naftopidil have higher affinities to alpha 1-adrenoceptors in the prostate than in the aorta. Some alpha 1-antagonists, such as prazosin and terazosin, are not selective with respect to alpha 1-adrenoceptor subtypes, while others, such as 5-methylurapidil and indoramin, show higher potencies for alpha 1C-adrenoceptors and much lower potencies for alpha 1A- and alpha 1B-subtypes. In conclusion, the recent findings from pharmacological and molecular biological studies indicate that selective antagonists of alpha 1C-adrenoceptors could be effective in the treatment of urinary obstruction in symptomatic BPH with fewer cardiovascular side effects.

Adrenergic alpha-Antagonists↗
PubMed1994

Phorbol ester-induced inhibition of GABA uptake by synaptosomes and by Xenopus oocytes expressing GABA transporter (GAT1).

We examined the effect of 12-O-tetradecanoylphorbol 13-acetate (TPA) on the sodium-dependent uptake of gamma-aminobutyric acid (GABA) by the synaptosomal fraction from rat cerebral cortex. Activation of protein kinase C (PKC) by 100 nM TPA inhibited the Na(+)-dependent uptake of GABA by 38.1%, whereas 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD), an inactive phorbol ester, did not alter the uptake. The inhibition was blocked by preincubation with 100 nM staurosporine, a potent inhibitor of PKC. The Eadie-Hofstee plots revealed the presence of a high affinity uptake system. The treatment with TPA increased the Km value from 6.76 microM to 18.5 microM with a trend toward a slight decrease of Vmax. In the presence of beta-alanine, TPA inhibited the GABA uptake by increasing the Km value from 8.65 microM to 15.0 microM without affecting Vmax. The molecular basis of the inhibitory effect of TPA was further examined using Xenopus oocytes expressing GAT1, a beta-alanine-insensitive and nipecotate-sensitive neuronal GABA transporter, resulting in a similar effect of TPA. The value of Km, but not Vmax, was increased by the treatment with 100 nM TPA. These results suggest that PKC may modulate the GABA uptake into presynaptic terminals through the inhibition of GAT1 activity.

Alkaloids↗
PubMed1994

Production of specific antibodies against GABA transporter subtypes (GAT1, GAT2, GAT3) and their application to immunocytochemistry.

Polyclonal subtype-specific antibodies were developed against three subtypes of GABA transporters (GAT1, GAT2 and GAT3). By immunoblot analysis, each antibody detected a single band that could be blocked by absorption of the antibody with the respective antigen. GAT2 was found in various tissues, while GAT1 and GAT3 were detected only in the brain. GAT1 was distributed throughout the brain with the highest amount in the olfactory bulb, CA3 region of the hippocampus, layer I of the cerebral cortex, piriform cortex, superior colliculus, interpeduncular nucleus and nucleus spinal tract of the trigeminal nerve, while the GAT3 was densely found in the olfactory bulb, thalamus, hypothalamus, pons and medulla, globus pallidus, central gray, substantia nigra, deep cerebellar nuclei and nucleus spinal tract of the trigeminal nerve but not in the hippocampus, cerebral cortex, caudate-putamen and cerebellar cortex. GAT2 immunoreactivity was faint throughout the brain but was concentrated in the arachnoid and ependymal cells. Both GAT1 and GAT3 were found in the neuropil but not in the cell bodies nor in the white matter. These results suggest that GAT1, GAT2 and GAT3 are expressed in different cells and that GAT1 and GAT3 are involved in distinct GABAergic transmission while GAT2 may be related to non-neuronal function.

Amino Acid Sequence↗
PubMed1994

Effect of heat shock on intracellular calcium mobilization in neuroblastoma x glioma hybrid cells.

The effect of heat shock on agonist-stimulated intracellular Ca2+ mobilization and the expression of heat shock protein 72 (hsp72) in neuroblastoma x glioma hybrid cells (NG 108-15 cells) were examined. Hsp72 was expressed at 6 h after heat shock (42.5 degrees C, 2 h), reached a maximum at 12 h, and decreased thereafter. Bradykinin-induced [Ca2+]i rise was attenuated to 28% of control by heat shock at 2 h after heat shock, and reversion to the control level was seen 12 h later. When the cells were treated with quercetin or antisense oligodeoxyribonucleotide against hsp72 cDNA, the synthesis of hsp72 was not induced by heat shock, whereas bradykinin-induced [Ca2+]i rise was abolished and the [Ca2+]i rise was not restored. Recovery from this stressed condition was evident when cells were stimulated by the Ca(2+)-ATPase inhibitor thapsigargin, even in the presence of either quercetin or antisense oligodeoxyribonucleotide. Inositol 1,4,5-trisphosphate (IP3) production was not altered by heat shock at 12 h after heat shock, whereas IP3 receptor binding activity was reduced to 45.3%. In the presence of quercetin or antisense oligodeoxyribonucleotide, IP3 receptor binding activity decreased and reached 27.2% of the control 12 h after heat shock. Our working thesis is that heat shock transiently suppresses the IP3-mediated intracellular Ca2+ signal transduction system and that hsp72 is involved in the recovery of bradykinin-induced [Ca2+]i rise.

Animals↗
PubMed1994

Comparative study on alpha 1-adrenoceptor antagonist binding in human prostate and aorta.

1. Specific binding of [3H]-prazosin in prostatic and aortic membranes of humans was saturable and of high affinity (prostate: apparent dissociation constant, Kd = 0.35 +/- 0.03 nmol/L; aorta: Kd = 0.26 +/- 0.03 nmol/L). The density of [3H]-prazosin binding sites (Bmax) for prostate and aorta was 546 +/- 31 and 61.6 +/- 1.6 fmol/mg protein, respectively. 2. Prazosin, YM617, naftopidil and urapidil competed with [3H]-prazosin for the binding sites in a dose-dependent manner in the prostate and aorta of humans. The binding affinities of these antagonists in both tissues were compared, based on the inhibition constant, Ki. Both prazosin and urapidil showed similar affinity to [3H]-prazosin binding sites in human tissue, whereas YM617 and naftopidil showed approximately a 12 and two times higher affinity, respectively, to alpha 1-adrenoceptor sites of prostate than aorta. 3. The chloroethylclonidine treatment reduced partially the Bmax values for specific [3H]-prazosin binding in the prostate and aorta of humans with little effect on the Kd values. 4. These data suggest that YM617 is a relatively selective antagonist of human prostatic alpha 1-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1994

[Development of L-threo-DOPS, a norepinephrine precursor amino acid].

threo-Dihydroxyphenylserine (DOPS) is a synthetic amino acid which can be decarboxylated by L-aromatic amino acid decarboxylase to yield natural form of norepinephrine (l-NE), a principal neurotransmitter in both central and peripheral (sympathetic) nervous systems. Like L-Dopa as an agent for dopamine precursor therapy, DOPS was expected to have a potential as an agent for NE precursor therapy. Previous studies carried out by several groups in early 1970s, however, reached a negative conclusion that threo-DOPS was not an effective precursor of NE in the brain because of its low NE-increasing activity and weak pharmacological action. Since the latter half of 1970s, on the contrary, three Japanese research groups have successfully shown the possibility of DOPS as a useful NE-precursor. That is, Tanaka (Kobe Univ.) showed that L-threo-DOPS is the real l-NE precursor among four DOPS-enantiomers, and that it has several pharmacological activities such as a slow-onset and long-lasting pressor effect, an inhibitory effect on harmaline-induced tremor and so on. Hayashi and Suzuki (Osaka Univ.) found through the mobility study on familial amyloid polyneuropatchy (FAP) that the progress of the disease develops NE-deficiency (NE-D), that severe orthostatic hypotention in FAP might be due to NE-D, and that L-DOPS has favorable effects on this symptom. Narabayashi (Juntendo Univ.) found that NE-D develops in patients with advanced Parkinson's disease (PD), that a freezing phenomenon in these patients might be associated with NE-D, and that L-DOPS improves the phenomenon. Based on these findings, the development of L-DOPS for registration had been undertaken by Sumitomo Pharmaceuticals Co., and an approval was given to it in 1989 as an agent for the treatment orthostatic hypotention in FAP or Shy-Drager syndrome and freezing phenomenon in PD. Preclinical and clinical studies done in the R&D confirmed that L-DOPS markedly restored NE-D and improved related-syndrome in the NE-deficient animals/patients, and that its actions were slow-onset, long-lasting and gentle. The R & D of L-DOPS described in this paper includes studies on industrial production, efficacy pharmacology (mode of action), metabolism and clinical trial of this agent.

Amyloid Neuropathies↗
PubMed1993

Isolation and characterization of SSE1 and SSE2, new members of the yeast HSP70 multigene family.

Two new members of the Saccharomyces cerevisiae heat-shock protein 70 multigene (HSP70) family were isolated from a yeast expression library using antisera made against a yeast calmodulin-binding fraction. They are designated as SSE1 and SSE2, because their predicted amino acid (aa) sequences are highly homologous to each other (76% identical), and share homology with known members of the yeast HSP70 multigene family, but their homologies (13 to 28% identity) are not high enough to place them in known subfamilies. SSE1 and SSE2 are thought to encode polypeptides of 693 aa with calculated M(r)'s of 77,408 and 77,619, respectively. The SSE1 mRNAs were moderately abundant during steady-state growth at 23 degrees C, and increased a few-fold upon upshift to 37 degrees C. SSE2 mRNAs were present at low level during steady-state growth at 23 degrees C, and greatly increased upon upshift to 37 degrees C. Disruption of SSE1 results in slow-growing cells at any temperature. No phenotypic effects of the mutation in SSE2 were detected, and the growth property of the sse1sse2 double mutant was the same as that of the sse1 single mutant.

Amino Acid Sequence↗
PubMed1993

Inhibitory modulation of long-term potentiation via the 5-HT1A receptor in slices of the rat hippocampal dentate gyrus.

Modulation of long-term potentiation (LTP) and isoproterenol-induced long-lasting potentiation (ILLP) via the 5-HT1A receptor was examined in slice preparations of the rat hippocampal dentate gyrus. 8-OH-DPAT, a selective agonist of the 5-HT1A receptor, decreased population spike (PS) amplitude in these preparations, in a dose-dependent manner. Application of NAN-190, an antagonist of the 5-HT1A receptor, blocked the 8-OH-DPAT-induced decrease in PS amplitude. LTP was not affected by application of 8-OH-DPAT during tetanic stimulation (TS), while in contrast, application of NAN-190 during TS significantly augmented LTP. The NAN-190-induced enhancement of LTP was reversed by 8-OH-DPAT. In addition, a dose-dependent inhibition of isoproterenol-induced long-lasting potentiation was produced by simultaneous application of 8-OH-DPAT and isoproterenol. These results suggests that 5-HT modulates LTP in the hippocampal dentate gyrus via the 5-HT1A receptor, in an inhibitory fashion.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Detection of the FK506-FKBP-calcineurin complex by a simple binding assay.

[3H]FK506-FK506-binding protein (FKBP) complex does not bind polyethyleneimine-treated glass fiber filters, on the other hand, it binds the filter when it makes a complex with calcineurin. This enabled us to develop a simple binding assay to detect the FK506-FKBP-calcineurin complex in the mixture and to estimate the amount of FKBP or calcineurin which can form the complex in the soluble extracts from rat tissues. The molar concentration of FKBP of every rat tissue is much higher than that of calcineurin, and FKBP/calcineurin molar ratio varies from 13 to 33 in various brain regions, and from 42 to 343 in peripheral tissues. These results suggest that most of the FKBP molecules have physiological roles which are not related to calcineurin, in spite of their potential ability to form the complex with FK506 and calcineurin.

Animals↗
PubMed1993

Down-regulation by retinoic acid of the catalytic subunit of protein phosphatase type 2A during granulocytic differentiation of HL-60 cells.

Activity of protein phosphatase measured in the absence of divalent cations was decreased by 50% during all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation into the granulocytic phenotype. Treatment of HL-60 cells with ATRA led to a dramatic decrease in the amount of protein phosphatase type 2A (PP2A) protein, whereas that of protein phosphatase type 1 (PP1) protein was relatively constant, as detected by immunoblotting with antibodies specific to PP1 and PP2A. The decreased phosphatase activity may be mainly due to a decrease in the expression of the PP2A protein. The mRNA level of PP2A beta was markedly decreased within 5 h after addition of ATRA, but there was only a slight increase in the mRNA level of PP2A alpha. Selective down-regulation of PP2A beta mRNA clearly preceded the cell differentiation induced by ATRA treatment. Thus, PP2A is down-regulated during ATRA-induced differentiation of HL-60 cells into granulocytes.

Cell Differentiation↗
PubMed1993

Cellular and intracellular localization of epsilon-subspecies of protein kinase C in the rat brain; presynaptic localization of the epsilon-subspecies.

The cellular and intracellular localization of the epsilon-subspecies of protein kinase C (PKC) in the rat brain was demonstrated by immunocytochemistry using specific antibodies against epsilon-PKC. The epsilon-PKC-specific immunoreactivity was most abundant in the hippocampal formation, olfactory tubercle and Calleja's islands, was moderate in the cerebral cortex, anterior olfactory nuclei, accumbens nucleus, lateral septal nuclei and caudate-putamen and low in the thalamus and medulla. The epsilon-PKC-immunoreactivity was scanty in the perikarya, except for the pyramidal cells of CA3 region of the hippocampus and the immunoreactivity was mainly present in neuropils and nerve fibers. The distribution of epsilon-PKC immunoreactive neurons was consistent with that obtained by in situ hybridization histochemistry. Electron microscopic observations of the hippocampus revealed that the epsilon-PKC is predominantly present in the cytoplasm of axon and nerve terminals and that this enzyme is associated with mitochondrial membrane and vesicles. These results suggested that epsilon-PKC is probably involved in presynaptic functions in CNS, perhaps even neurotransmitter release.

Amino Acid Sequence↗
PubMed1993

Differential changes in serotonin 5-HT1A and 5-HT2 receptor binding in patients with chronic schizophrenia.

Serotonin 5-HT1A and 5-HT2 receptors were examined in the postmortem brains of controls and patients with chronic schizophrenia. In the prefrontal cortex from patients with schizophrenia, 5-HT1A receptor binding was increased, while 5-HT2 receptor binding was decreased, when compared to controls. The increased 5-HT1A receptor binding or the decreased 5-HT2 receptor binding was observed in both the patients who had been medicated with neuroleptics at time of death and those who had not, at least 2 months prior to death. Thus, abnormalities of 5-HT receptor subtypes seem to exist in the brains of patients with chronic schizophrenia. 5-HT related agents might be beneficial for the treatment of schizophrenia.

Chronic Disease↗
PubMed1993

Thapsigargin induces an endothelium-dependent, intracellular calcium ion-dependent vasodilation in vitro.

The effect of thapsigargin, a specific inhibitor of intracellular Ca(2+)-ATPases, on endothelium-dependent relaxation was studied in the guinea pig thoracic aorta. Thapsigargin (1 nM-1 microM) produced a concentration-dependent relaxation of aortic strips precontracted by phenylephrine (0.1 microM) in the presence and absence of extracellular Ca2+. Thapsigargin (0.1 microM-10 microM) produced the concentration-dependent contraction in aortic strips with no endothelium in the presence and absence of extracellular Ca2+. The relaxant effect of thapsigargin (1 microM) was not attained in a de-endothelialised aortic strip. NG-nitro-L-arginine (10 nM-0.1 mM), a blocker of NO synthase, produced a concentration-dependent inhibition of thapsigargin-induced relaxation. Thapsigargin failed to produce vasodilation by pretreatment of aortic strips with NG-nitro-L-arginine (10 microM). Thapsigargin (1 microM) increased tissue levels of guanosine 3', 5' cyclic-monophosphate in aortic strips preincubated with phenylephrine (0.1 microM). The results suggest that the intracellular Ca2+ mobilization in endothelial cells by thapsigargin is of significance in the endothelium-dependent relaxation of guinea pig thoracic aorta.

Animals↗
PubMed1993

Immunocytochemical localization of alpha-, beta I-, beta II- and gamma-subspecies of protein kinase C in the motor and premotor cortices of the rhesus monkey.

We obtained evidence for the localization of alpha-, beta I-, beta II- and gamma-subspecies of protein kinase C (PKC) in the monkey motor and premotor cortices (Brodmann's areas 4 and 6). In Brodmann's area 4, the immunoreactivity for the alpha-PKC was present in horizontal and round cells in the layers I and II, and small pyramidal cells in layer III and also in the glial cells in subcortical white matter. The alpha-PKC immunopositive glial cells contained GFAP-immunoreactive product. The beta I-PKC immunoreactivity was present in the round cells in layer I and in the pyramidal cells in the layer V, including Betz cells. The beta II-PKC immunoreactivity was observed as small dots in perikarya of the small and medium-sized pyramidal cells in layers II, III, V and VI, but not in layer I. The gamma-PKC immunoreactive cell bodies were observed in layers II, III and VI, and most of the immunoreactive cells were pyramidal. Intense gamma-PKC immunoreactivity was found in the neuropils of layers I and II. Similar distributions of four PKC subspecies were seen in Brodmann's area 6, except that beta I-PKC immunoreactive Betz cells were not present. The unique localization of PKC subspecies suggested that each PKC subspecies was involved in the specific function in motor and premotor cortices of the rhesus monkey.

Animals↗
PubMed1993

Immunohistochemical localization of gamma-aminobutyric acid- and aspartate-containing neurons in the guinea pig superior olivary complex.

The immunohistochemical localization of gamma-aminobutyric acid (GABA)- and aspartate-containing neurons was demonstrated in the guinea pig superior olivary complex, using purified antisera to GABA and aspartate, respectively. Medium-sized oval GABA-containing neurons were found in the lateral superior olive, and bipolar medium-sized GABA-containing neurons were observed in the dorsal hilus of the lateral superior olive. Medium-sized to large round GABA-containing neurons were observed in the ventral nucleus of the trapezoid body. GABA-containing terminals were found throughout the superior olivary complex with the highest density in the ventral nucleus of the trapezoid body. Aspartate-like immunoreactivity was observed in medium-sized round or oval neurons in the lateral superior olive, small fusiform neurons in the ventral nucleus of the trapezoid body, fusiform medium-sized neurons in the medial superior olive and oval medium-sized neurons in the superior paraolivary nucleus and round medium-sized neurons in the medial nucleus of the trapezoid body. Double staining method demonstrated that aspartate-containing neurons in the medial nucleus of the trapezoid body were surrounded by GABA-containing terminals. The present results suggested the possible origin of GABAergic and aspartatergic olivocochlear bundles.

Animals↗
PubMed1993

FKBP12-FK506 complex inhibits phosphatase activity of two mammalian isoforms of calcineurin irrespective of their substrates or activation mechanisms.

The interaction of calcineurin (Ca2+/calmodulin-dependent protein phosphatase) with the potent immunosuppressive agent FK506 and its 12 kDa isoform binding protein (FKBP12) was investigated. The FKBP12-FK506 complex inhibited the Ca2+/calmodulin-stimulated phosphatase activity of each of two calcineurin isoforms, which contain either the catalytic subunit A alpha or A beta (calcineurin A alpha or A beta) of bovine calcineurin. Calcineurin phosphatase activity was inhibited by the FKBP12-FK506 complex irrespective of the substrate or the enzyme activation mechanism. FK506 and FKBP-12 inhibited calcineurin in a concentration-dependent manner, and complete inhibition of the phosphatase activity appeared to require a molar excess of FKBP12-FK506 complex. Immunochemical measurements revealed tissue differences in the concentration of calcineurin, which may be of importance to the selectivity for immunosuppression of all of the biological effects. Direct binding studies with [3H]dihydro-FK506 suggest that the ratio of FKBP12-FK506 complex to calcineurin in vivo when IL2 production is inhibited is well correlated with the ratio when calcineurin phosphatase activity is inhibited in vitro. These results suggest that calcineurin is a relevant cellular target of FK506 when bound to FKBP-12.

Amino Acid Sequence↗