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Y Fujitani

Publications and source records attributed to Y Fujitani.

At least 55 records · Page 3Linked to original sources
PubMed1994

Transcriptional activation of the IL-6 response element in the junB promoter is mediated by multiple Stat family proteins.

IL-6 signals activate an IL-6 response element in the junB promoter, JRE-IL6, in a Ras-independent manner. IL-6 rapidly induced a DNA-binding activity to the Ets binding site of JRE-IL6 (JEBS), one of necessary DNA motifs of the IL-6 response element. The IL-6-induced JEBS-binding activity was indistinguishable from those to acute phase response element (APRE) in both kinetics of induction and its DNA-binding specificity. Purified APRE binding factors (APRFs) from IL-6-stimulated rat liver were found to be composed of multiple Stat3-related proteins and Stat1. Moreover the purified APRFs specifically made a complex with JRE-IL6 with the same mobility as that observed in the crude extracts. These results indicate that an immediate early signal of IL-6 leading to activation of JRE-IL6 is mediated by STAT family transcription factors.

Animals↗
PubMed1994

Inhibition of the cardiac protein kinase A-dependent chloride conductance by endothelin-1.

Endothelin-1 is a peptide hormone constitutively secreted by vascular and endocardial endothelial cells. Secretion of endothelin-1 is increased under certain pathophysiological conditions, including coronary vasospasm, cardiac ischaemia and myocardial infarction. We have examined the effect of endothelin-1 on the protein kinase A (PKA)-dependent chloride current in voltage-clamped guinea pig ventricular myocytes. This conductance, induced by catecholamines through beta-adrenergic receptors, counteracts the simultaneously increased L-type calcium current by shortening the action potential duration. We report here that endothelin-1, acting through ETA (endothelin-1-selective) receptors, inhibited the current through a pertussis toxin-sensitive mechanism, analogous to muscarinic receptors, by reducing the intracellular cyclic AMP concentration. This effect of endothelin-1 should help protect the ventricle against potentially arrhythmogenic shortening of the action potential during ischaemia when the circulating levels of catecholamines are increased.

Animals↗
PubMed1994

ETA and ETB receptors on single smooth muscle cells cooperate in mediating guinea pig tracheal contraction.

We investigated the distribution of endothelin A (ETA) and ETB receptors in single smooth muscle cells and their contribution to ET-induced contractions of guinea pig trachea. ETA and ETB receptors were detected in smooth muscle membranes (maximum binding capacities of 810 and 360 fmol/mg protein and dissociation constants of 38 and 5.1 pM for 125I-labeled ET-1 and 125I-ET-3, respectively) and visualized autoradiographically in primary cultured cells. ET-1 and ET-3 evoked concentration-dependent increases in intracellular Ca2+ concentration and smooth muscle tension. The half-maximally effective concentrations of ET-1 and ET-3 at inducing contractions were 1.9 and 2.7 nM, respectively. The Ca2+ responses showed tachyphylaxis to both ETs after stimulation with ET-1, but only to ET-3 after stimulation with ET-3. Consecutive applications of ET-3 and ET-1 (10 nM each) classified the cells into ETA dominant (approximately 30%) responding to only ET-1, ETB dominant (approximately 20%) responding to only ET-3, and ETA- and ETB-possessing (approximately 50%) cells responding to both. The ETA antagonist, 10 microM BQ-123, attenuated ET-1-induced contractions but did not affect the ET-3-induced contractions. The results indicate that both receptors coexist in a major population of smooth muscle cells and cooperate in mediating ET-1-induced contractions.

Animals↗
PubMed1993

Identification of a novel interleukin-6 response element containing an Ets-binding site and a CRE-like site in the junB promoter.

Interleukin-6 (IL-6) activation of the immediate-early gene junB has been shown to require both a tyrosine kinase and an unknown 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7)-sensitive pathway. Here we report the identification and characterization of an IL-6 immediate-early response element in the junB promoter (designated JRE-IL6) in HepG2 cells. The JRE-IL6 element, located at -149 to -124, contains two DNA motifs, an Ets-binding site (EBS) (CAGGAAGC) and a CRE-like site (TGACGCGA). Functional studies using variously mutated JRE-IL6 elements showed that both motifs were necessary and sufficient for IL-6 response of the promoter. The EBS of the JRE-IL6 element (JEBS) appears to bind a protein in the Ets family or a related protein which could also form a major complex with the EBSs of the murine sarcoma virus long terminal repeat or human T-cell leukemia virus type 1 long terminal repeat. The CRE-like site appears to weakly bind multiple CREB-ATF family proteins. Despite the similarity in the structure between the JRE-IL6 element and the polyomavirus enhancer PyPEA3, composed of an EBS and an AP1-binding site and known to be activated by a variety of oncogene signals, JRE-IL6 could not be activated by activated Ha-Ras, Raf-1, or 12-O-tetradecanoylphorbol-13-acetate. We show that IL-6 activates JRE-IL6 through an H7-sensitive pathway that does not involve protein kinase C, cyclic AMP-dependent kinase, Ca(2+)- or calmodulin-dependent kinases, Ras, Raf-1, or NF-IL6 (C/EBP beta). The combination of JEBS and the CRE-like site appears to form the basis for the selective and efficient response of JRE-IL6 to IL-6 signals, but not to signals generated by activated Ha-Ras, Raf-1, or protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

A selective agonist of endothelin type B receptor, IRL 1620, stimulates cyclic GMP increase via nitric oxide formation in rat aorta.

The signal transduction pathways of endothelin (ET)-induced vasorelaxation in rat aorta were investigated. An agonist for ETB receptors, IRL 1620, induced transient increases in cytosolic Ca++ (peak at about 10 sec) and cyclic GMP (peak at about 20 sec) accompanied by transient vasorelaxation (peak at about 60 sec) in aortic strips precontracted with 100 nM norepinephrine. The cyclic GMP content was increased 3- to 6-fold from the basal level (1.6 +/- 0.2 fmol/micrograms of protein) with 1 nM to 1 microM IRL 1620. The cyclic GMP elevation was endothelium-dependent, abolished in the presence of 100 microM NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, and recovered after the further addition of 1 mM L-arginine. An ETB receptor antagonist, IRL 1038 (3 microM), inhibited completely the cyclic GMP increase induced by 100 nM IRL 1620 (8.1 +/- 0.6 fmol/micrograms of protein) without affecting the basal level. On the other hand, an ETA receptor antagonist, 3 microM BQ-123, enhanced significantly both the basal level (3.7 +/- 0.6 fmol/micrograms of protein) and the IRL IRL 1620-induced production (12.2 +/- 0.8 fmol/micrograms of protein) of cyclic GMP. Specific binding sites for [125I]IRL 1620 were detected in rat aortic membranes with a dissociation constant of 37.0 pM and maximal binding capacity of 36.6 fmol/mg of protein, which disappeared after removing the endothelium. Unlabeled ET-1, ET-3, IRL 1620 and IRL 1038, but not BQ-123, displaced the binding of [125I]IRL 1620 with inhibitory constants of 38.5 pM, 36.6 pM, 97.8 pM and 8.9 nM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1992

An endothelin B receptor-selective antagonist: IRL 1038, [Cys11-Cys15]-endothelin-1(11-21)

In the inhibition of specific binding of [125I]endothelins (ETs) to membrane from various tissues of rats, guinea pigs, pigs and humans, [Cys11-Cys15]-ET-1(11-21), IRL 1038, has a much higher affinity for ETB receptors (Ki = 6-11 nM) than for ETA receptors (Ki = 0.4-0.7 microM). In contraction assays, with ET-3 as a stimulant, 3 microM IRL 1038 antagonized the ETB receptor-mediated contraction of guinea pig ileal and tracheal smooth muscle without any significant agonistic activity, but did not effect the ETA receptor-mediated contraction of rat aortic smooth muscle. IRL 1038 is therefore, considered to be the first antagonist selective to the ETB receptor.

Amino Acid Sequence↗
PubMed1992

A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor.

A series of C-terminal linear peptides of endothelin (ET)-1 and their N alpha-succinyl (Suc) analogs were synthesized and their binding affinities for the two subtypes of ET receptor, ETA and ETB, in porcine lung membranes were examined. Among the synthetic analogs, Suc-[Glu9,Ala11,15]-ET-1(8-21), IRL 1620, was the most potent and specific ligand for the ETB receptor (KiETA/KiETB approximately equal to 120,000) as judged by the Ki values for ETA (1.9 microM) and ETB (16 pM) receptors. IRL 1620 was 60 times more selective for the ETB receptor than ET-3 (KiETA/KiETB approximately equal to 1,900). IRL 1620 (10(-9)-10(-7) M) induced contractions of the guinea pig trachea with a comparable potency to those of ET-1 or ET-3, suggesting that IRL 1620 is a potent ETB receptor agonist.

Amino Acid Sequence↗
PubMed1992

Endothelin stimulates both cAMP formation and phosphatidylinositol hydrolysis in cultured embryonic bovine tracheal cells.

Embryonic bovine tracheal (EBTr) cells were found to possess receptors for endothelin (ET) of ET-1-selective (ETA) subtype with a Kd for ET-1 of 114 pM and a Bmax of 12.9 fmol/10(5) cells. Stimulation of EBTr cells with 100 pM to 100 nM ET-1 increased the contents of both inositol phosphates and cAMP in a concentration-dependent manner, indicating that the receptors are coupled to both phosphatidylinositol hydrolysis and cAMP formation in EBTr cells.

Animals↗
PubMed1992

Autocrine receptors for endothelins in the primary culture of endothelial cells of human umbilical vein.

Human umbilical vein endothelial cells (HUVECs) in primary culture produced and secreted endothelin 1 (ET-1) actively. Specific binding of [125I]ET-1 to these cells was not detectable because of the saturation of ET receptors with endogenously produced ET-1. However, addition of phosphoramidon, an inhibitor of ET-converting enzyme, to the medium reduced the production of ET-1 and thus the receptors on HUVECs were made available for exogenously added [125I]ET-1. Binding studies using phosphoramidon-treated HUVECs indicated the existence of a non-isopeptide-selective type (ETB) of ET receptor with a Kd of 17 pM. This receptor is thought to be involved in ET-induced vasodilation in an autocrine manner in vivo.

Binding Sites↗
PubMed1991

Comparison in postnatal development between somatosensory and motor conduction in rabbits.

A comparative study between the somatosensory-evoked cerebral potential (SEP) and motor cortex-evoked muscle response (MEMR), and between the sensory nerve action potential (SNAP) and peripheral nerve-evoked muscle response (M wave) was performed with respect to their maturational changes in the peak latencies, using 24 rabbits of ages of 10 to 180 days. The peak latencies of SEP, MEMR, SNAP and the M wave all decreased with an increase in age according to a hyperbolic curve of y = axb + c (b less than 0). The adult values of the peak latencies were reached simultaneously at 80 days of age for SEP and MEMR, and at 60 days of age for SNAP and the M wave. These findings indicate that the conduction of the somatosensory and motor pathways becomes fully maturated at the same time. On analysis of the differential coefficients on the above equation, some but substantial differences in the decrease rate of the peak latency were also found between SEP and MEMR, and between SNAP and the M wave. This suggests that there are also some differences in the maturational rate between the two pathways.

Action Potentials↗
PubMed1991

Epigenetic control of tumor cell morphology.

XC cell line derived from a single rat cell transformed by the Prague strain of Rous sarcoma virus produced morphologically different colonies. Among them, two distinct cell types consisting of thick, fusiform cells (L-type), and of flat, polygonal cells (R-type) were apparent. By repeated subclonings, pure cultures, L1 and R1, respectively, were obtained. These clones underwent morphological conversion during prolonged culture; L-type colonies appeared in the R-type clone and vice versa. The kinetic curve suggested that the conversion was multi-stepped. When inoculated into nude mice, L-type cells produced much larger tumors at a higher frequency than R-type cells, and the tumors induced by these two clones were histologically different. The expression of v-src gene was higher in L-type than in R-type cells at both mRNA and protein levels.

Actins↗
PubMed1990

Concentric electrodes for producing acupuncture-like anesthetic effects.

We designed concentric electrodes composed of a center electrode and an outer ring electrode. Electrical stimulation with two sets of such electrodes for 15 min as conditioning stimuli was given to the left hand of 35 adult subjects to induce acupuncture-like anesthetic effects. The effects immediately after the conditioning were compared between stimulation through a pair of center electrodes alone at 3 Hz (conditioning 1) and simultaneous stimulation of 3 Hz through a pair of center electrodes and 100 Hz through a pair of outer ring electrodes (conditioning 2). In conditioning 2, modulating effects of 100 Hz stimuli through a pair of outer ring electrodes made it possible to increase the voltage strength of 3 Hz stimuli through a pair of center electrodes with maintaining the minimum perception of pricking sensation. In both conditioning procedures, muscle twitching was not accompanied. It was found that the respective stimulating current thresholds for faint touch sensation and also for pricking sensation at the right forearm could be elevated significantly more by conditioning 2 (1.54 and 1.40 times) than by conditioning 1 (1.20 and 1.14 times).

Acupuncture Analgesia↗
PubMed1989

Identification of puberty-accelerating pheromones in male mouse urine.

Gas chromatography-mass spectrometry was employed to identify the two volatile amines in male mouse urine. These amines were much less concentrated in urine of castrated males. The identified amines, isobutylamine and isoamylamine, were assayed for the potential of puberty acceleration in postweaning female mice. A total of 105 young female mice were exposed to one of the following five odors: distilled water (control), 0.1 M isobutylamine, 0.1 M isoamylamine, a mixture of 0.05 M isobutylamine and 0.05 M isoamylamine, or fresh male mouse urine. The mixture of these amines accelerated the vaginal opening of young females. Except for the control, all experimental odors accelerated the first vaginal estrus in ICR strain mice.

Amines↗
PubMed1989

Histological evidence of natural killer cell aggregation against malignant melanoma induced by adoptive immunotherapy with lymphokine-activated killer cells.

Adoptive immunotherapy with lymphokine-activated killer (LAK) cells and systemic administration of recombinant Interleukin-2 (RIL-2) was carried out in a case of malignant melanoma with lung metastases. Histological specimens from the lung showed a metastatic melanoma heavily invaded by atypical lymphoid cells with convoluted nuclei of varying size. Immunohistochemistry revealed that these cells had the characteristic exclusively of natural killer cell (Leu-7+). Nodules of these cells mimicked the appearance of non-Hodgkin's lymphoma of pleomorphic type. Molecular cytogenetic analysis, however, showed the absence of rearranged bands for the T-cell receptor beta-chain gene, indicating the absence of T-cell clones. At autopsy, 1 month after the LAK therapy, the heavy invasion of convoluted cells had disappeared. These findings clearly indicate that the LAK cell plus RIL-2 therapy induced Leu-7+ lymphoid cells, phenotypically suggestive of natural killer cell aggregation in the tumours.

Cell Aggregation↗