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Biomedical subjects

I Kojima

Publications and source records attributed to I Kojima.

At least 145 records · Page 8Linked to original sources
PubMed1991

Involvement of protein kinase C in angiotensin II-mediated release of 12-hydroxyeicosatetraenoic acid in bovine adrenal glomerulosa cells.

The present study was conducted to determine whether protein kinase C was involved in angiotensin II-mediated release of 12-hydroxyeicosatetraenoic acid (12-HETE) from bovine adrenal glomerulosa cells. Activators of protein kinase C, 12-O-tetradecanoylphorbol 4-acetate (TPA) and 1-oleoyl-2-acetylglycerol (OAG), significantly increased release of 12-HETE. The effect of OAG was potentiated by BAYK8644, a stimulator of calcium entry. Sphingosine, H-7 and staurosporine, which inhibited the activity of protein kinase C in vitro, almost completely blocked 12-HETE release induced by TPA. These agents also significantly reduced angiotensin II-mediated 12-HETE release. When time course of the liberation of 12-HETE was measured, angiotensin II elicited sustained release of 12-HETE, which was inhibited by staurosporine. These results indicate that angiotensin II induces sustained release of 12-HETE, a feed forward regulator of aldosterone secretion, and that protein kinase C may be involved in this process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Inhibition of growth hormone secretion by activin A in human growth hormone-secreting tumour cells.

Effect of activin A on growth hormone secretion was studied in primary culture of 8 human GH-secreting adenomas, which were responsive to TRH in vivo. When studied in vitro, basal GH secretion was reduced in all cases when cells were pre-incubated for 48 h with activin A at a concentration of 5 X 10(-9) mol/l or greater. Pretreatment of GH-secreting cells with 1 X 10(-9) mol/l activin A did not affect either basal secretion or cellular content of GH. These tumour cells also responded to TRH in vitro and the GH response to TRH was completely blocked in cells pretreated with activin A. Activin A slightly reduced the increase in cytoplasmic free calcium concentration induced by TRH. Furthermore, pretreatment of the cells with activin A attenuated GH secretion induced by A23187 or 12-O-tetradecanoyl phorbol-4-acetate, agents which bypass receptor-mediated generation of second messengers. These results indicate that activin A inhibits GH secretion by directly acting on human GH-secreting cells and that activin A inhibits the action of TRH by acting on multiple steps in the messenger system.

Activins↗
PubMed1990

Insulin-like growth factor-I stimulates diacylglycerol production via multiple pathways in Balb/c 3T3 cells.

We previously reported that insulin-like growth factor-I (IGF-I) induced sustained calcium cycling across the plasma membrane in primed competent Balb/c 3T3 cells (Kojima, I., Matsunaga, H., Kurokawa, K., Ogata, E., and Nishimoto, I. (1989) J. Biol. Chem. 263, 16561-16567). The present study was conducted to examine whether IGF-I affected cellular metabolism of 1,2-diacylglycerol (1,2-DAG). In primed competent cells prelabeled with [3H]myristate, 1 nM IGF-I caused a 50% increase in [3H]DAG within 10 min. This increase in [3H]DAG was accompanied by 1) a decrease in radioactivity in the glycosylphosphatidylinositol fraction in [3H]glucosamine-labeled cells and a concomitant increase in [3H]inositol-glycan, and 2) a decrease in [3H]phosphatidylcholine and a concomitant elevation of [3H]phosphorylcholine in [3H]choline-labeled cells. When [3H]choline-labeled cells were treated with 10 nM 12-O-tetradecanoylphorbol-4-acetate (TPA), [3H]phosphatidylcholine was reduced by 50%. The TPA-induced reduction of [3H]phosphatidylcholine was completely blocked by 50 microM sphingosine and 50 microM H-7, inhibitors of protein kinase C. Both sphingosine and H-7 attenuated IGF-I-mediated reduction of [3H]phosphatidylcholine. In addition, treatment with IGF-I for 3 h or more resulted in sustained increase in 1,2-DAG mass, which was attenuated by cycloheximide. The increase in DAG mass was accompanied by enhanced incorporation of [14C]glucose into 1,2-DAG. These results indicate that, in primed competent Balb/c 3T3 cells, IGF-I stimulates 1,2-DAG production via multiple pathways and that IGF-I may induce breakdown of phosphatidylcholine by a mechanism involving protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Studies on the cell-cycle dependency of the actions of insulin-like growth factor-I in Balb/c 3T3 cells.

The present study was conducted to determine the cell-cycle dependency of various actions of IGF-I in Balb/c 3T3 cells. When autophosphorylation of the IGF-I receptor was determined in [32P]-labelled cells, IGF-I increased radioactivity in a 100 K-Da phosphoprotein, presumably beta-subunit of the IGF-I receptor, both in quiescent and in primed competent cells. Likewise, IGF-I stimulated uptake of [3H]deoxyglucose independent of the cell cycle. In contrast, IGF-I increased calcium entry, radioactivity in [3H]diacylglycerol, and [3H]thymidine incorporation in primed competent cells while these reactions were not induced by IGF-I in quiescent cells. The latter three reactions were attenuated when cells were pretreated with pertussis toxin. These results indicate that some, but not all, of the actions of IGF-I are dependent on the cell cycle in Balb/c 3T3 cells. They also suggest that a pertussis-toxin-sensitive G protein may be involved in the cell-cycle-dependent actions of IGF-I.

Animals↗
PubMed1990

Difference in sensitivity to glucagon action in three different rat liver systems.

We compared sensitivity to glucagon in three different rat liver systems. In perfused liver, half-maximal response of glycogenolysis was obtained by 5 x 10(-11) mol/L glucagon. In contrast, half-maximal response was obtained by 10(-9) mol/L glucagon in batch incubation of isolated hepatocytes. In perifusion system using the same isolated hepatocytes, 9 x 10(-11) mol/L glucagon induced half-maximal response. In both perfused liver and perifusion system, dose response relationships for glucagon-induced cyclic adenosine monophosphate (cAMP) output were identical. In batch incubation of isolated hepatocytes, again much higher concentration of glucagon was needed to increase cAMP output. Inhibitors of glucagon degradation did not increase the sensitivity of hepatocytes in batch incubation system. When the liver was perfused in recirculation system, glycogenolytic response to glucagon was significantly less than when it was perfused in flow-through system. Also, when extract of lipophilic substances in conditioned medium of batch incubation system was included in perfusate, the glycogenolytic response to glucagon was diminished in perfused liver system. In contrast to the action of glucagon, sensitivities of hepatocytes to calcium mobilizing hormones, phenylephrine, and angiotensin II, in three systems were nearly identical. These results suggest that the diminished sensitivity of hepatocytes to glucagon observed in batch incubation system is due, at least in part, to a substance (or substances) released from hepatocytes.

Angiotensin II↗
PubMed1990

Mechanism of prostaglandin E2-induced glucose production in rat hepatocytes.

Effects of prostaglandin E2 (PGE2) on glycogenolysis were examined in rat hepatocytes. In a batch incubation system using isolated hepatocytes, PGE2 increased glucose output dose-dependently. The glycogenolytic effect of PGE2 was detected at a concentration of 10(-11) M, and 10(-8) M PGE2 elicited the maximum glucose output, which was equal to that by glucagon. PGE2 did not increase cAMP at any dose tested (10(-11)-10(-4) M). Instead, PGE2 increased the cytoplasmic free calcium concentration ([Ca2+]c). When the effect of PGE2 on [Ca2+]c was studied in aequorin-loaded cells, the effect of PGE2 on [Ca2+]c was detected at 10(-12) M, and the magnitude of the response increased in a dose-dependent manner. PGE2 increased [Ca2+]c even in the presence of 1 microM extracellular calcium, suggesting that PGE2 mobilizes calcium from an intracellular pool. In line with these observations, PGE2 increased the production of inositol trisphosphate. Compared with the action of PGE2, 16,16-dimethyl-PGE2, a PGE2 analog, was less potent in stimulating glycogenolysis. These results indicate that PGE2 stimulates glycogenolysis by activating the calcium messenger system.

16,16-Dimethylprostaglandin E2↗
PubMed1990

In vitro responsiveness of aldosterone-producing adenoma to angiotensin II, K and ACTH.

In vitro responsiveness to various stimulators of aldosterone secretion was studied in a perifusion system using slices obtained from three aldosterone-producing adenomas (APAs), three adjacent nontumorous glands and three normal adrenal glands. All three APA tissues responded to angiotensin II, K and ACTH in vitro. Angiotensin II (10 nM), K (12 mM) and ACTH (10 nM) caused more than a 2-fold increase in aldosterone secretion. The sensitivity of APA tissues to angiotensin II was identical to that in normal adrenal cortex. In slices obtained from APA, angiotensin II induced rapid increases in [3H]inositol and [45Ca] efflux, both of which preceded the aldosterone response. These results suggest that APA cells have an almost normal transducing system to stimulators of aldosterone secretion.

Adenoma↗
PubMed1989

Platelet-derived growth factor stimulates synthesis of 1,2-diacylglycerol from monoacylglycerol in Balb/c 3T3 cells.

1,2-Diacylglycerol (1,2,-DAG) plays an important role in the protein kinase C-mediated signal-transduction system. Several reports have shown that 1,2-DAG is generated through various pathways other than classical phospholipid hydrolysis. We observed a rapid incorporation of [3H]myristate into 1,2-DAG in platelet-derived-growth-factor (PDGF)-treated Balb/c 3T3 cells. [14C]Palmitate was similarly incorporated into 1,2-DAG. The effect of PDGF, which was inhibited by cycloheximide, became maximal after 60 min treatment with PDGF, and disappeared 300 min after removal of PDGF. Treatment with triacylglycerol lipase revealed that labelled saturated fatty acid was incorporated into the sn-1 position. PDGF barely stimulated incorporation of [3H]glycerol or [14C]glucose into 1,2-DAG. Incorporation of [3H]myristate into 1,2-DAG preceded that into triacyglycerol and phospholipids. These results suggest that synthesis of 1,2-DAG from monoacylglycerol is enhanced in PDGF-treated cells. However, there is no significant difference in the activity of monoacylglycerol acyltransferase measured in vitro in quiescent and PDGF-treated cells. The reason for this discrepancy is discussed.

Acyltransferases↗
PubMed1989

A stimulatory effect of somatostatin: enhancement of activin A-mediated FSH secretion in rat pituitary cells.

The interaction between somatostatin and activin A was studied in terms of FSH secretion in rat pituitary cells in primary culture. Incubation of pituitary cells with 1 nM activin A for 48 hrs resulted in an increase in FSH release into incubation medium. The effect of activin A was dependent on cell-density and the higher the density, the smaller the stimulatory action of activin A. Somatostatin, by itself, did not affect the FSH secretion. When 100 nM somatostatin was included together with activin A or the cells were pretreated with somatostatin for 2 hrs, the activin A-induced FSH secretion was enhanced. This potentiation effect of somatostatin was inversely dependent on the cell-density. These results indicate that somatostatin enhances, rather than inhibits, the activin A action in pituitary cells.

Activins↗
PubMed1989

Dual effect of activin A on cell growth in Balb/c 3T3 cells.

Effects of activin A on cell growth were studied in Balb/c 3T3 cells. When incubated with serum, activin A inhibited serum-induced increase in DNA synthesis in a concentration-dependent manner. Activin A also inhibited serum-induced increase in cell number. When added in quiescent cells, activin A did not affect competence-inducing activity of PDGF. Activin A by itself had a small competence-inducing activity. In contrast, when added in competent cells, activin A inhibited progression activity of platelet-poor plasma. These results indicate that activin A has dual action on cell proliferation in Balb/c 3T3 cells.

Activins↗
PubMed1989

Calcium rather than cyclic AMP is an intracellular messenger of parathyroid hormone action on glycogen metabolism in isolated rat hepatocytes.

The synthetic 1-34 fragment of human parathyroid hormone (1-34hPTH) stimulated glucose production in isolated rat hepatocytes. The effect of 1-34hPTH was dose-dependent and 10(10) M-1-34 hPTH elicited the maximum glucose output, which was approx. 80% of that by glucagon. Although 1-34hPTH induced a small increase in cyclic AMP production at concentrations higher than 10(-9) M, 10(-10) M-1-34hPTH induced the maximum glucose output without significant elevation of cyclic AMP. This is in contrast to the action of forskolin, which increased glucose output to the same extent as 10(-10) M-1-34hPTH by causing a 2-fold elevation of cyclic AMP. In addition to increasing cyclic AMP, 1-34hPTH caused an increase in cytoplasmic free calcium concentration ([Ca2+]c). When the effect of 1-34hPTH on [Ca2+]c was studied in aequorin-loaded cells, low concentrations of 1-34hPTH increased [Ca2+]c: the 1-34hPTH effect on [Ca2+]c was detected at as low as 10(-12) M and increased in a dose-dependent manner. 1-34hPTH increased [Ca2+]c even in the presence of 1 microM extracellular calcium, suggesting that PTH mobilizes calcium from an intracellular pool. In line with these observations, 1-34hPTH increased the production of inositol trisphosphate. These results suggest that: (1) PTH activates both cyclic AMP and calcium messenger systems and (2) PTH stimulates glycogenolysis mainly via the calcium messenger system.

Animals↗
PubMed1989

Na-Ca exchanger as a calcium influx pathway in adrenal glomerulosa cells.

When aequorin-loaded glomerulosa cells were incubated in isotonic Na2+-free medium containing N-methyl-D-glucamine instead of NaCl, there was an increase in cytoplasmic free calcium concentration, [Ca2+] c, which was not observed when extracellular calcium concentration was reduced to 1 microM. Upon removal of extracellular sodium, there was nearly five-fold increase in fractional efflux ratio of calcium. The reduction of extracellular sodium resulted in a stimulation of calcium influx rate, the magnitude of which was dependent on extracellular sodium concentration. Similar stimulation of calcium influx was observed when extracellular sodium was replaced with lithium. Nitrendipine did not affect the calcium influx induced by the reduction of extracellular sodium while a derivative of amiloride 3',4'-dichlorobenzamil, which inhibits Na-Ca exchange, attenuated calcium influx observed in sodium-free medium. These results indicate that removal of extracellular sodium leads to an increase in [Ca2+] c by stimulating calcium influx and that calcium enters the cell via Na-Ca exchanger.

Aequorin↗
PubMed1989

Stimulation of insulin secretion by transforming growth factor-beta.

Effects of transforming growth factor-beta (TGF-beta) on insulin secretion were studied in rat pancreatic islets. When islets were incubated in a batch incubation system with various concentrations of TGF-beta in the presence of 2.8 mM glucose, TGF- beta increased insulin release in a concentration-dependent manner. Both TGF- beta 1 and TGF- beta 2 were equally effective. The stimulatory action of TGF- beta was greater in the presence of stimulatory concentration of glucose. In perifusion system, TGF- beta induced an immediate monotonic increase in insulin secretion. These results indicate that TGF- beta is a stimulator of insulin secretion.

Animals↗
PubMed1989

Ambient C1- ions modify rat mesangial cell contraction by modulating cell inositol trisphosphate and Ca2+ via enhanced prostaglandin E2.

Our recent observation showed that angiotensin II (AII) and arginine vasopressin (AVP) stimulate Ca2+-activated Cl- conductance in mesangial cells. These data raise the possibility that mesangial cell function may be modulated by extracellular chloride concentration [( Cl-]o). The present study was undertaken to test this possibility using cultured rat mesangial cells. When the [Cl-]o was reduced to zero, the percentage of mesangial cells showing contraction responding to AII and AVP was decreased from 72 +/- 9 to 33 +/- 10% and from 60 +/- 4 to 24 +/- 11%, respectively. Ca2+ transients induced by AII and AVP, measured in mesangial cells loaded with Ca2+-sensitive photoprotein aequorin, were attenuated as [Cl-]o decreased. Also, when [Cl-]o decreased, inositol trisphosphate (IP3) levels of mesangial cells were suppressed, both in the presence and absence of AII or AVP. PGE2 production by mesangial cells increased when [Cl-]o decreased and the effects of ambient Cl- deprivation could be restored by addition of indomethacin to the Cl- -free medium. Moreover, PGE2 decreased mesangial cell contractility, Ca2+ transients, and IP3 production in response to AII and AVP. These data suggest that the decrease in [Cl-]o attenuates mesangial cell contraction by suppressing IP3 production and thus Ca2+ transients in response to AII and AVP through enhanced PGE2 production.

Angiotensin II↗
PubMed1989

Stimulation of glucose production by activin-A in isolated rat hepatocytes.

The effect of activin-A on glycogenolysis was studied in isolated rat hepatocytes. Activin-A stimulated glucose output in hepatocytes in a dose-dependent manner. The maximal effect of the glycogenolytic action of activin-A, which was about 50% of the glucagon action, was obtained at 10(-9) M. When 10(-9) M activin-A 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(-9) M activin-A and 10(-8) M angiotensin-II were added. Activin-A did not increase cAMP at any doses tested, but induced a rapid increase in cytoplasmic free calcium concentration. Activin-A increased the cytoplasmic free calcium concentration even in the presence of 1 microM extracellular calcium, suggesting that activin-A caused calcium release from an intracellular calcium pool(s). The internal calcium pool affected by activin-A appeared to be the same as that affected by either angiotensin-II or vasopressin. When [3H] inositol-labeled hepatocytes were incubated with activin-A, radioactivity in the inositol trisphosphate fraction was rapidly increased. These results indicate that activin-A acts on rat hepatocytes and stimulates glycogenolysis by activating the calcium messenger system.

Activins↗
PubMed1989

[Calcium influx: an intracellular message of the mitogenic action of insulin-like growth factors].

Insulin-like growth factor-I and II (IGF-I and II) are potent progression factors. In BALB/c 3T3 cells, IGFs exert the progression activity when quiescent cells are pretreated with platelet-derived growth factor and epidermal growth factor. In this IGF-responsive state, which we designated primed competent state, IGF-I and II stimulate calcium influx. The IGF-stimulated calcium influx sustains for at least few hours and is dependent on extracellular calcium concentration. To stimulate calcium influx IGF activates calcium-permeable cation channel. This IGF-sensitive channel is voltage-independent and is not totally selective for calcium. When IGF-mediated calcium influx is inhibited by either reduction of extracellular calcium or by adding cobalt or tetramethrin, IGF-induced DNA synthesis is attenuated. In either case, stimulation of calcium influx rate correlates quite well with the increase in DNA synthesis. Moreover, when calcium influx is augmented pharmacologically in primed competent cells by using BAY K8644, DNA synthesis is increased. These results suggest that calcium influx is an intracellular message of the mitogenic action of IGF-I and II.

Animals↗