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Biomedical subjects

I Kojima

Publications and source records attributed to I Kojima.

At least 127 records · Page 7Linked to original sources
PubMed1993

Modulation of growth of vascular smooth muscle cells by activin A.

Activin A is a homodimeric protein structurally related to transforming growth factor-beta. The present study was conducted to examine the effect of activin A on the growth of rat vascular smooth muscle cells (VSMC) in culture. When serum-deprived cells were incubated with activin A, nuclear labeling of bromodeoxyuridine occurred after a 12-h lag period. The effect of activin A on nuclear labeling was dose-dependent, being maximal at 10(-9) M. Activin A also increased the number of VSMC after 30 h of incubation. Insulin-like growth factor-1 (IGF-1) had only a small effect on nuclear labeling by itself but the effects of IGF-1 and activin A were additive. When quiescent VSMC were treated with activin A for 4 h, the effect of subsequent IGF-1 was markedly enhanced. Furthermore, activin A induced an autocrine production of IGF-1 in VSMC. In contrast to these positive effects on cell growth, activin A was rather inhibitory to the action of IGF-1 in activin-primed cells. In addition, activin A inhibited platelet-derived growth factor-induced nuclear labeling. These results indicate that activin A modifies growth of VSMC by complex mechanisms involving autocrine production of IGF-1 and modification of the action of IGF-1.

Activins↗
PubMed1993

Role of calcium fluxes in the action of glucagon on glucose metabolism in rat hepatocytes.

The aim of the present study was to assess the role of calcium fluxes in the action of glucagon on glycogenolysis and gluconeogenesis in isolated rat hepatocytes. Calcium influx was blocked by two ways: by use of the compound tetramethrin and by reduction of extracellular calcium to 1 microM. The minimal concentration of tetramethrin that inhibited glucagon-mediated calcium entry was 7.5 x 10(-7) M. In the presence of 7.5 x 10(-7) M tetramethrin, glucagon-induced glycogenolysis was markedly attenuated when glucagon concentration was 10(-9) M or higher. In contrast, tetramethrin had no effect on glucogenolysis evoked by lower concentrations of glucagon. Similarly, tetramethrin greatly reduced gluconeogenesis induced by high concentrations of glucagon without affecting the effect of low concentrations of glucagon. The same results were obtained in the presence of 1 microM extracellular calcium. To abolish glucagon-induced elevation of cytoplasmic free calcium concentration, we heavily loaded quin2 into hepatocytes. In these cells, glycogenolysis evoked by low concentrations of glucagon was completely abolished. Glycogenolysis caused by high concentrations of glucagon was markedly inhibited. These results indicate that glucagon action on hepatic glucose metabolism is mediated by two different mechanisms, which depend on concentrations of glucagon.

Aminoquinolines↗
PubMed1993

Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes.

The present study was conducted to examine the effect of activin A on growth of rat hepatocytes. EGF induced a 10-fold increase in DNA synthesis as assessed by [3H]thymidine incorporation in cultured hepatocytes. When activin A was added together with EGF, DNA synthesis induced by EGF was markedly inhibited. Inhibition was detected at a concentration of 10(-10) M, and 5 x 10(-9) M activin A almost completely blocked EGF-mediated DNA synthesis. Similarly, activin A completely blocked DNA synthesis induced by hepatocyte growth factor/scatter factor. Activin A was capable of inhibiting EGF-mediated DNA synthesis, even when added 36 h after the addition of EGF. With the same time interval, TGF-beta also blocked EGF-induced DNA synthesis. Although both activin A and TGF-beta inhibited growth of hepatocytes in a similar manner, either activin A or TGF-beta did not compete with each other in their binding when assessed by competitive binding using an iodinated ligand. When hepatocytes were incubated with EGF, release of bioactivity of activin A into culture medium was detected after 48 h or later. Activity of activin A was released from parenchymal cells but not from nonparenchymal cells. mRNA for beta A subunit of activin was detected only slightly in unstimulated hepatocytes, but markedly increased at 48 h after the addition of EGF. To determine whether endogenously produced activin A affects DNA synthesis, we examined the effect of follistatin, an activin-binding protein that blocks the action of activin A. An addition of follistatin significantly enhanced EGF-induced DNA synthesis. Finally, in partial hepatectomized rat, expression of mRNA for beta A subunit in liver was markedly increased 24 h after the partial hepatectomy. These results indicate that activin A inhibits initiation of DNA synthesis in hepatocytes by acting on its own receptor and that activin A acts as an autocrine inhibitor of DNA synthesis in rat hepatocytes.

Activins↗
PubMed1993

Activin A inhibits cell-cycle progression induced by insulin-like growth factor-I in Balb/c 3T3 cells.

The present study was carried out to examine the effect of activin A on cell-cycle progression induced by insulin-like growth factor-I (IGF-I) in Balb/c 3T3 cells. When activin A was added together with IGF-I to competent cells primed with epidermal growth factor (primed competent cells), both [3H]thymidine incorporation and nuclear labelling induced by IGF-I were inhibited. The inhibition was concentration-dependent and the maximum inhibition was obtained with 1 nmol activin A/1. To ascertain the time in which activin A exerted its inhibitory action, we divided 12 h, the time required for primed competent cells to progress towards the S phase, into four periods and activin A was added during each of the four periods. It was effective when added during either the second (3 to 6 h) or the third period (6 to 9 h) but it did not affect cell-cycle progression when added during the first (0 to 3 h) or the last period (9 to 12 h). We then examined whether activin A affected intracellular events elicited by IGF-I. It did not affect either autophosphorylation of the IGF-I receptor or calcium entry induced by IGF-I. Likewise, it did not cause any change in the radioactivity of 1,2-diacylglycerol (DAG) in cells prelabelled with [3H]myristate while the increase in the mass of DAG induced by IGF-I was markedly reduced by activin A. The dose-response relationship for the activin A-mediated reduction of DAG mass correlated well with th at for the activin A-mediated reduction of DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1993

[Growth factors in the pituitary gland].

There are increasing numbers of evidence that many factors, such as growth factors and cytokines, exist in the pituitary gland, and modulate the release of pituitary hormone both in vivo and in vitro. They indicate the importance of autocrine and paracrine control system within the pituitary gland. For instance, activin, a compound whose existence and nature (in contrast to the related protein inhibin) was not contemplated before its discovery in 1986, has been shown to be synthesized in gonadotrophs and to produce diverse effects on the anterior pituitary. We would like to introduce some recent studies on growth factors in the pituitary gland.

Activins↗
PubMed1992

Stimulation of glucose transport by guanine nucleotides in permeabilized rat adipocytes.

Effects of guanine nucleotides on glucose transport were studied in permeabilized rat epididymal fat cells. GTP gamma S and Gpp(NH)p, but not App(NH)p, stimulated 3-O-methylglucose transport. Effect of GTP gamma S was dose-dependent, being detectable at 0.1 mM, and 1.0 mM GTP gamma S stimulated glucose transport to the same extent as insulin. GTP gamma S (0.3 mM) enhanced insulin-stimulated glucose transport while 1 mM GTP gamma S did not affect insulin-mediated transport. GDP beta S had no effect on glucose transport by itself but rather enhanced insulin action. NaF, which is known to activate trimeric G proteins, increased glucose transport to the same extent as insulin. Likewise, mastoparan augmented glucose transport. These results indicate that a certain type of trimeric G protein(s) is involved in the regulation of glucose transport.

3-O-Methylglucose↗
PubMed1992

Pertussis toxin blocks activin A-induced production of inositol phosphates in rat hepatocytes.

The present study was conducted to examine an involvement of G protein in the action of activin A in rat parenchymal liver cells. Activin A induced a dose-dependent increase in inositol phosphates in cells prelabelled with [3H]inositol. The effect of activin A was completely blocked by pretreatment of the cells with pertussis toxin. In contrast, pertussis toxin had little effect on angiotensin II-induced production of inositol phosphates. Both activin A and angiotensin II inhibited glucagon-mediated production of cAMP. Pretreatment of the cells with pertussis toxin blocked the inhibition induced by both activin A and angiotensin II. In permeabilized cells, activin A augmented production of inositol phosphates. Activin-mediated production of inositol trisphosphate was enhanced by GTP-gamma S and was attenuated by GDP-beta S. These results suggest that a pertussis toxin-sensitive G protein(s) may be involved in the action of activin A in hepatocytes.

Activins↗
PubMed1992

[The calcium messenger system].

Calcium ion acts as an intracellular messenger of various types of extracellular signals including hormones, neurotransmitters, cytokines and growth factors. Recent advances in the research of the calcium messenger system have provided informations as to the structure and function of many proteins involved in the messenger system. Also, technical advances in the measurement of the dynamics of calcium ion in a small cell have made it possible to better understand the role of calcium in the activation of the cell. In the present review, a picture of the calcium messenger system is presented.

Calcium↗
PubMed1992

Effects of activin A and somatostatin on intact FSH secretion and intracellular Ca2+ concentration in human FSH-secreting pituitary adenoma cells.

Activin A stimulated synthesis and secretion of intact FSH in dispersed human FSH-secreting adenoma cells. Significant stimulation was observed after 24 hr. Activin A caused an increase in Ca2+ concentration ([Ca2+]i). This response occurred soon after the activin A action. These effects were blocked in Ca(2+)-deficient medium and by nitrendipine (5 microM). Somatostatin inhibited the activin A-induced intact FSH secretion and the [Ca2+]i response. These findings indicated that Ca2+ influx through voltage-gated Ca2+ channel was involved in the activin A induced synthesis and secretion of intact FSH.

Activins↗
PubMed1992

Isoflavonoids, genistein, psi-tectorigenin, and orobol, increase cytoplasmic free calcium in isolated rat hepatocytes.

Isoflavonoid compounds, genistein, psi-tectorigenin and orobol have been implicated as inhibitors of tyrosine-specific protein kinase and phosphatidylinositol turnover. These compounds have been frequently used as a pharmacological tool to assess signal transduction pathways in various cell systems. In the course of analyzing signaling pathways in rat hepatocytes, we obtained an unexpected finding that these compounds transiently increase cytoplasmic free calcium. Since the Ca2+ mobilizing effect was observed in 1 microM calcium containing buffer, the source of the Ca2+ may be intracellular stores. Thus, when interpreting data obtained using these compounds, caution is needed.

Aequorin↗
PubMed1992

Oscillation of cytoplasmic free calcium concentration induced by insulin-like growth factor I.

The effect of insulin-like growth factor I (IGF-I) on cytoplasmic free calcium concentration ([Ca2+]c) was studied in single BALB/c 3T3 cells by monitoring fura-2 fluorescence. In primed competent cells, IGF-I (1 nM) increased [Ca2+]c in approximately 60% of the cells tested. IGF-I-mediated elevation of [Ca2+]c was observed after a 4- to 17-min lag period. Elevation of [Ca2+]c was only transient but was followed by repetitive increases in [Ca2+]c. The interval between each peak was quite constant in each cell at a given concentration of IGF-I. When the concentration of IGF-I was reduced, both the latent period and interval of each peak were prolonged, whereas amplitude of the increase in [Ca2+]c was not altered. In medium containing 10 microM extracellular calcium, IGF-I did not cause any increase in [Ca2+]c. Likewise, blockade of IGF-induced calcium entry by either cobalt or tetramethrin abolished IGF-I action on [Ca2+]c. IGF-I-mediated oscillation was not affected by either ryanodine or caffeine, compounds that affect calcium-induced calcium release. In addition, pretreatment of the cell with neomycin did not affect IGF-I-mediated oscillation. In agreement with this, IGF-I did not augment production of [3H]inositol trisphosphate in cells prelabeled with [3H]inositol. These results indicate that IGF-I induces oscillation of [Ca2+]c in a single primed competent cell and that the oscillation is totally dependent on IGF-I-mediated calcium entry.

3T3 Cells↗
PubMed1991

Comparison of effects of HGF and EGF on cellular calcium in rat hepatocytes.

We compared the effects of HGF and EGF on cytoplasmic free calcium concentration, [Ca2+]c, and inositol trisphosphate production in rat hepatocytes. HGF induced a prompt and transient elevation of [Ca2+]c. EGF also induced an immediate increase in [Ca2+]c, the magnitude of which was greater than that by HGF. In contrast, in the presence of 1 microM extracellular calcium EGF increased [Ca2+]c to a lesser extent than HGF. When cells were pretreated with EGF, the effect of HGF on [Ca2+]c was greatly enhanced. However, such enhancement was not observed in medium containing 1 microM extracellular calcium. In hepatocytes prelabeled with [3H]-inositol, both HGF and EGF increased [3H]inositol trisphosphate. HGF and EGF acted synergistically to stimulate production of inositol trisphosphate. These results indicate that both HGF and EGF increase [Ca2+]c by a mechanism involving phosphoinositide turnover and that the actions of HGF and EGF on hepatocyte calcium metabolism are not totally identical.

Animals↗
PubMed1991

Mechanism of glycogenolytic action of histamine in rat hepatocytes.

The mechanism by which histamine induces glycogenolysis was investigated in rat hepatocytes. Histamine induced stimulation of glucose output in hepatocytes in a dose-dependent manner. The maximal effect of the glycogenolytic action of histamine, which was approximately 60% of the maximal glucagon action, was obtained at 10(-6) M. These effects were inhibited by H1 receptor antagonists triprolidine hydrochloride and tripelennamine but not by a H2 receptor antagonist cimetidine. Histamine also increased the activity of phosphorylase a. When 10(-6) M histamine and 5 x 10(-9) M glucagon were added simultaneously, the actions of these two agents were additive. In contrast, there was no additivity when 10(-6) M histamine and 10(-8) M angiotensin II were added. Histamine did not increase adenosine 3',5'-cyclic monophosphate at any doses tested but induced a rapid increase in the cytoplasmic free calcium concentration ([Ca2+]c). Histamine increased [Ca2+]c even in the presence of 1 microM extracellular calcium, an observation suggesting that histamine caused calcium release from an intracellular calcium pool(s). When [3H]inositol-labeled hepatocytes were incubated with histamine, radioactivity in the D-myo-inositol trisphosphate fraction was rapidly increased. These results indicate that histamine acts on rat hepatocytes mainly via H1 receptors and stimulates glycogenolysis by activating the calcium messenger system.

Angiotensin II↗
PubMed1991

Spot determinations of urinary cortisol for the screening of Cushing's syndrome.

The usefulness of spot determination of urinary cortisol in the screening of Cushing's syndrome was evaluated by measuring the cortisol concentration in randomly sampled urine in 68 normal subjects and in 9 patients with Cushing's syndrome. The urinary cortisol concentration in the morning was significantly higher in patients with Cushing's syndrome but some overlap existed between normal subjects and patients with Cushing's syndrome. In contrast, there was a clear discrimination between two groups when urinary cortisol was measured in the late evening: urinary cortisol was lower than 75 micrograms per gram creatinine (microgram/gCr) in normal subjects but higher than 150 micrograms/gCr in patients with Cushing's syndrome. When 1 mg dexamethasone was administered at 2300 h in the evening, spot urinary cortisol the next morning was less than 80 micrograms/gCr in normal subjects while it was above 100 micrograms/gCr in patients with Cushing's syndrome. Dexamethasone-induced suppression of urinary cortisol in normal subjects lasted until late in the afternoon, which allows sampling of urine at any time in the morning and possibly in the afternoon. These results suggest the usefulness of spot determination of urinary cortisol in the screening of Cushings' syndrome.

Adolescent↗