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Biomedical subjects

E Ogata

Publications and source records attributed to E Ogata.

At least 217 records · Page 12Linked to original sources
PubMed1989

Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] metabolism in vitamin D-deficient rats infused with 1,25-(OH)2D3.

Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g rat.day 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected [1 beta-3H]1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of [3H]24,25-(OH)2D3 to [3H]1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level. It is suggested that 24,25-(OH)2D3 plays a role in modifying serum 1,25-(OH)2D3 concentrations by affecting the metabolism of 1,25-(OH)2D3 and may have a therapeutic values in the treatment of hypercalcemia or hypercalciuria caused by 1,25-(OH)2D3 excess.

24,25-Dihydroxyvitamin D 3↗
PubMed1989

Suppression of serum 1,25-dihydroxyvitamin D in humoral hypercalcemia of malignancy is caused by elaboration of a factor that inhibits renal 1,25-dihydroxyvitamin D3 production.

Although many patients with humoral hypercalcemia of malignancy exhibit reduced serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels, N-terminal fragments of recently identified PTH-related protein as well as PTH itself elevate serum 1,25-(OH)2D concentrations. In the present study, the effect of tumor extracts from human tumor-implanted hypercalcemic nude rat models with high and low serum 1,25-(OH)2D on renal 1,25-(OH)2D3 production was examined using rat kidney cells in culture. Whereas tumors from rats with high serum 1,25-(OH)2D levels (OCC rats) contained only a single peak of cAMP production-stimulating activity (CPSA) in osteogenic sarcoma cells on reverse phase HPLC, tumor extracts from rats with low serum 1,25-(OH)2D levels (UCC rats) contained at least two peaks of CPSA. The main peak (peak A) was estimated to be approximately 17K by gel permeation chromatography, which was the same as the molecular size of the hitherto identified PTH-related protein, and a minor peak of CPSA (peak B) was estimated to be about 25K. When peak A or crude extracts of OCC tumors as well as human PTH-(1-34) were added to primary cultures of rat kidney cells, the production of 1,25-(OH)2D3 was significantly stimulated. In contrast, although peak B or crude UCC tumor extracts had no effect on 1,25-(OH)2D3 production in themselves, when they were added together with peak A or human PTH-(1-34) the stimulation of 1,25-(OH)2D3 production was almost completely inhibited. Both peak A and peak B enhanced cAMP production in cultured kidney cells, and the cAMP production by peak A was not affected by peak B. These results are consistent with the possibility that elaboration of an additional factor from tumor cells may be the mechanism by which serum 1,25-(OH)2D levels are suppressed in patients with humoral hypercalcemia of malignancy. The nature as well as the mechanism of action of this factor remain to be elucidated.

Animals↗
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

[Basic analysis of extracorporeal shock wave lithotripsy of gallstones].

Influence of extracorporeal shock wave lithotripsy (ESWL) on human gallstones placed in dog gallbladders was investigated. After irradiation of shock wave more than 600 times, maximal diameter of residual stones of 10 mm before irradiation was destroyed to 2 mm or less. Levels of serum transaminase (GOT.GPT) were elevated, in parallel with times of shock waves. These results suggested that 600 times of shock waves were enough to destroy one cholesterol stone, diameter of which was about 1 cm. Data of elevation of serum transaminase showed that more than 600 times of shock waves were possible to induce the damage of liver.

Alanine Transaminase↗
PubMed1988

Activin-A: a modulator of multiple types of anterior pituitary cells.

When primary culture of rat pituitary cells were incubated with 1 nM activin-A for more than 24 hrs, activin-A significantly increased intracellular content of FSH without affecting the control of LH. Pretreatment of the cells with activin-A also enhanced LHRH-induced FSH release without affecting LH release. Furthermore, pretreatment of the cells with activin-A significantly reduced both GRF-mediated GH release and TRH-mediated PRL release. However, activin-A did not affect the response of ACTH and TSH to their releasing hormones. These results indicate that, in addition to the known action on gonadotrophs, activin-A also modifies the function of somatotrophs and lactotrophs.

Activins↗
PubMed1988

Calcium influx: an intracellular message of the mitogenic action of insulin-like growth factor-I.

When G0-arrested BALB/c 3T3 cells were treated sequentially with platelet-derived growth factor and epidermal growth factor, cells became responsive to insulin-like growth factor-I (IGF-I). In these primed competent cells, 1 nM IGF-I elicited an approximately 3-fold increase in the calcium influx rate. IGF-I-induced calcium influx was relatively slow in onset and continued for at least 2 h in the presence of IGF-I. When a single Ca2+ channel current was studied by the patch-clamp technique using the cell-attached mode, inward currents with unitary conductance of 19 pS were observed in the presence of 1 nM IGF-I in the patch pipette. IGF-I-sensitive inward current was independent of membrane potential and was activated by a high concentration of insulin. Accordingly, 1 nM IGF-I caused a gradual increase in cytoplasmic free calcium concentration measured by fura2. The action of IGF-I on calcium influx was dependent on extracellular calcium, and IGF-I did not stimulate calcium influx when extracellular calcium concentration was reduced to 10 microM. Both cobalt and tetramethrin blocked the action of IGF-I on calcium influx without affecting the binding of 125I-IGF-I. In primed competent cells, IGF-I-stimulated [3H]thymidine incorporation was dependent on extracellular calcium and was attenuated by cobalt and tetramethrin. When cell-bound 125I-IGF-I was cross-linked by use of disuccinimidyl suberate, a 130-kDa protein was radiolabeled. Affinity labeling of the 130-kDa protein, presumably the alpha-subunit of the IGF-I receptor, was blocked by excess amount of unlabeled IGF-I. These results suggest that relatively low concentrations of IGF-I stimulate calcium influx in primed competent BALB/c 3T3 cells by activating a calcium-permeable cation channel via the IGF-I receptor and that calcium influx may be a critical intracellular message of the progression activity of IGF-I.

Affinity Labels↗
PubMed1988

[Reevaluation of direct radioimmunoassay for plasma cAMP concentration].

In order to evaluate the validity of the direct radioimmunoassay of plasma cAMP level by using Yamasa cyclic AMP assay kit, we determined the cyclic AMP concentration of normal human plasma before and after purification through anion-exchange chromatography. We found that 1) the direct assay before purification gave almost the same values as the indirect assay after purification by anion-exchange chromatography, 2) hemolysis did not affect the results of the direct assay, 3) the plasma cAMP was stable for up to 12 weeks when 5 mM EDTA was added to the blood at the time of sampling and stored below -20 degrees C and 4) the cAMP concentration did not decrease by repeated freeze-thawing of the plasma samples for up to 10 times. These results indicate that the direct radioimmunoassay of plasma cAMP concentration in normal subjects can give the same values as those obtained after purification by anion-exchange chromatography. Although further investigation is needed to clarify whether these results can be equally applied to patient's plasma with various diseases, the direct assay offers a convenient and accurate method to determine plasma cAMP concentration.

Blood Preservation↗
PubMed1988

A novel action of activin A: stimulation of insulin secretion in rat pancreatic islets.

The present study was conducted to examine an action of activin A on insulin secretion from rat pancreatic islets. In a batch incubation system, activin A stimulated insulin secretion in a dose-dependent manner at concentrations higher than 1 nM. Furthermore, activin A greatly potentiated glucose-induced insulin release. When islets were perifused with 1 nM activin A, insulin secretion was barely affected in this system. However, the insulin response to 16.7 mM glucose was greatly enhanced. Both the first and second phases of insulin response were enhanced by 1 nM activin A. These results indicate that, in addition to its known actions on pituitary-gonadal and hematopoietic systems, activin A modulates the function of pancreatic islets and stimulates insulin secretion.

Activins↗
PubMed1988

Expression of parathyroid hormone-related protein in a human T cell lymphotrophic virus type I-infected T cell line.

We analyzed human T cell lymphotrophic virus type I (HTLV-I)-infected T cells for the presence of mRNA coding for parathyroid hormone-related protein (PTHrP) by Northern blotting using synthetic DNA probes. We report here that PTHrP mRNAs were detected in a HTLV-I-infected T cell line, MT-2, but not in uninfected T cell or B cell lines, and that PTH-like bioactivity was detected only in the conditioned medium of MT-2 cells. Our study suggests that the pathophysiology of hypercalcemia in patients with adult T cell leukemia/lymphoma may resemble that which occurs with solid tumors.

Cell Line↗
PubMed1988

Evidence that type II insulin-like growth factor receptor is coupled to calcium gating system.

In competent Balb/c 3T3 cells primed with epidermal growth factor (primed competent cells), insulin-like growth factor-II (IGF-II) stimulated calcium influx in a concentration dependent manner with the ED50 of 450 pM. When receptor-bound [125I]IGF-II was cross-linked by use of disuccinimidyl suberate, a 240 K-Da protein was radiolabeled. Excess amount of unlabeled IGF-II inhibited the affinity-labeling of the 240 K-Da protein. To further examine whether IGF-II stimulates calcium influx by acting on the type II IGF receptor, we employed polyclonal antibody raised against rat type II IGF receptor, R-II-PABl. This antibody immunoprecipitated the type II IGF receptor and inhibited IGF-II binding in Balb/c 3T3 cell membrane without affecting IGF-I binding. In primed competent cells, R-II-PABl elicited an agonistic action in stimulating [3H]thymidine incorporation. Under the same condition, R-II-PABl elicited a marked stimulation of calcium influx. These results suggest that, in Balb/c 3T3 cells, 1) relatively low concentrations of IGF-II act mainly on the type II IGF receptor; 2) the type II IGF receptor is coupled to a calcium gating system; and 3) binding of a ligand to the type II IGF receptor leads to the stimulation of DNA synthesis.

Animals↗
PubMed1988

Evidence of cyclic AMP-independent action of glucagon on calcium mobilization in rat hepatocytes.

Glucagon increases the cytoplasmic free calcium concentration as measured by aequorin bioluminescence. It has been proposed by Wakelam et al. (Nature 323 (1986) 68-71) that low concentrations of glucagon mobilize calcium from an intracellular pool by causing polyphosphoinositide breakdown. To identify whether cyclic AMP mediates changes in the cytoplasmic free calcium concentration ([Ca2+]c) induced by glucagon, the effects of forskolin and exogenous cyclic AMP on [Ca2+]c were compared with that of glucagon in aequorin-loaded hepatocytes. Although the magnitudes of the [Ca2+]c responses to 250 microM forskolin and 1 mM 8-bromo cyclic AMP were identical to that of 5 nM glucagon, these two agents induced a more prolonged elevation of [Ca2+]c. Glucagon-induced elevation of [Ca2+]c was accompanied by a smaller increase in cyclic AMP than that induced by forskolin. When the cyclic AMP response to glucagon was potentiated by an inhibitor of phosphodiesterase, 3-isobutyl-1-methylxanthine, the glucagon-induced increase in [Ca2+]c was not affected. Conversely, when the cyclic AMP response to glucagon was reduced by pretreatment of the cells with angiotensin II, glucagon-induced changes in [Ca2+]c were rather enhanced. Furthermore, vasopressin potentiated glucagon-induced changes in [Ca2+]c despite the reduction of the cyclic AMP response to glucagon. In the presence of 1 microM extracellular calcium, angiotensin II did not enhance glucagon-induced changes in [Ca2+]c. These results suggest that at least part of the action of 5 nM glucagon on calcium mobilization is independent of cyclic AMP.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 metabolism in calcium-deficient rats.

The effect of 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] on 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] metabolism was examined in rats fed on a low-calcium diet. These rats exhibit hypocalcaemia, high urinary cyclic AMP excretion, a markedly elevated serum 1,25(OH)2D concentration and low serum concentrations of both 24,25(OH)2D and 25(OH)D. When the rats are treated orally with 1, 5 or 10 micrograms of 24,25(OH)2D3/100 g every day, there is a dramatic decrease in serum 1,25(OH)2D concentration in a dose-dependent manner concomitant with an increase in serum 24,25(OH)2D concentration. Serum calcium concentration and urinary cyclic AMP excretion are not significantly affected by the 24,25(OH)2D3 treatment, which suggests that parathyroid function is not affected by the 24,25(OH)2D3 treatment. The 25(OH)D3 1 alpha-hydroxylase activity measured in kidney homogenates is markedly elevated in rats on a low-calcium diet but is not affected by any doses of 24,25(OH)2D3. In contrast, recovery of intravenously injected [3H]1,25(OH)2D3 in the serum is decreased in 24,25(OH)2D3-treated rats. Furthermore, when [3H]1,25(OH)2D3 is incubated in vitro with kidney or intestinal homogenates of 24,25(OH)2D3-treated rats there is a decrease in the recovery of radioactivity in the total lipid extract as well as in the 1,25(OH)2D3 fraction along with an increase in the recovery of radioactivity in the water-soluble phase. These results are consistent with the possibility that 24,25(OH)2D3 has an effect on 1,25(OH)2D3 metabolism, namely that of enhancing the degradation of 1,25(OH)2D3. However, because a considerable proportion of the injected 24,25(OH)2D3 is expected to be converted into 1,24,25(OH)3D3 by renal 1 alpha-hydroxylase in 24,25(OH)2D3-treated rats, at least a part of the decrease in serum 1,25(OH)2D concentration may be due to a competitive inhibition by 24,25(OH)2D3 of the synthesis of 1,25(OH)2D3 from 25(OH)D3. Thus the physiological importance of the role of 24,25(OH)2D3 in regulating the serum 1,25(OH)2D concentration as well as the mechanism and metabolic pathway of degradation of 1,25(OH)2D3 remain to be clarified.

24,25-Dihydroxyvitamin D 3↗
PubMed1988

Effects of secretin on content of PGE2 and 6-keto PGF1 alpha in gastric mucosa.

To determine the involvement of prostaglandins in the action of secretin on the promotion of the healing process in injured gastric mucosa, the effect of secretin infusion on the content of PGE2 and 6-keto PGF1 alpha (a major metabolite of PGI2) in human gastric mucosa was investigated. Specimens of both normal and injured mucosa were obtained from each of the patients who underwent polypectomy a week prior to the study. The specimens were obtained before and 20 min after intravenous infusion of secretin [2 Crick, Harper and Raper (CHR) units/kg] or saline. The basal content of PGE2 in injured mucosa was three times higher than that in normal gastric mucosa. Secretin did not increase the PGE2 content of normal gastric mucosa. However, secretin induced a sevenfold increase in the PGE2 content of injured mucosa. The content of 6-keto PGF1 alpha was not affected by secretin. These results suggest that, in injured mucosa, PGE2 is involved in the healing process and in the action of secretin as well.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

A hypercalcemic nude rat model that completely mimics human syndrome of humoral hypercalcemia of malignancy.

Tumors causing humoral hypercalcemia of malignancy (HHM) were implanted to athymic nude rats. In one of these rat models transplanted with uterine cancer (UCC), a complete reproduction of human HHM syndrome was achieved: hypercalcemia, hypophosphatemia with increased urinary phosphate and cyclic AMP excretion, and suppressed serum 1,25-dihydroxy-vitamin D (1,25(OH)2D) level. In another hypercalcemic nude rat model implanted with oral cavity cancer (OCC), all the features were similar except for markedly elevated serum 1,25(OH)2D. Hypercalcemia disappeared by surgical removal of the tumors in both models, confirming the humoral mechanisms for causing these features. Furthermore, in UCC tumor-bearing rats, hypophosphatemia, increased renal phosphate excretion, and reduced serum 1,25(OH)2D concentration were already present when these rats were only marginally hypercalcemic. These results raise the possibility that the changes in renal tubular phosphate handling and vitamin D metabolism in HHM are not secondary to hypercalcemia but are due to direct effects of the humoral factor(s) that cause this syndrome. Extracts of both tumors exhibited stimulation of cyclic AMP production in osteoblastlike cells, UMR 106, which could be almost completely inhibited by parathyroid hormone (PTH) antagonist, human PTH(3-34). By comparing the nature and characteristics of humoral factor(s) from UCC and OCC models, mechanisms responsible for causing these abnormalities can be explored. Thus, these nude rat models can be useful for elucidating the underlying mechanism of the development of HHM.

Animals↗
PubMed1988

Requirement of GTP on somatostatin-induced K+ current in human pituitary tumor cells.

The role of GTP on somatostatin-induced K+ current increase was examined in dissociated human pituitary tumor cells obtained from three acromegalic patients. Pituitary cells in culture were voltage-clamped by using the patch clamp technique in the whole-cell configuration. Somatostatin (100 nM) increased the membrane permeability to K+ ions and inhibited hormone secretion. A current-voltage relation of the somatostatin-induced K+ current showed an inward rectification when the concentration of extracellular K+ ions was increased. The amplitude of the somatostatin-induced K+ current decreased during recording when the patch pipette solution did not contain GTP; addition of 100 microM GTP to the patch pipette solution prevented this reduction. Intracellular application of 100 microM guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S] evoked an inward rectifying K+ conductance in the absence of somatostatin. After the GTP[gamma S]-induced K+ conductance reached a steady level, application of somatostatin did not further increase the K+ conductance. In pertussis toxin-treated cells GTP[gamma S] did not evoke K+ conductance. It was concluded that somatostatin-induced K+ channels were regulated by a GTP-binding protein.

Acromegaly↗
PubMed1988

Activation of a calcium-permeable cation channel by insulin-like growth factor II in BALB/c 3T3 cells.

Insulin-like growth factor II (IGF II) is a member of somatomedin family and is a potent mitogen in various types of mammalian cells. We have recently reported that IGF II stimulates calcium influx in competent BALB/c 3T3 cells primed with epidermal growth factor (J. Biol. Chem. 262: 12120-12126, 1987). Using patch-clamp technique, we show here an IGF II-sensitive cation channel in BALB/c 3T3 cell plasma membrane. Calcium is permeable to this cation channel and its opening behavior is independent of membrane potential. IGF II increases the opening probability of the identical channel in cells pretreated sequentially with platelet-derived growth factor and epidermal growth factor, whereas IGF II does not affect the opening of the channel in G0-arrested cells. This cation channel activity is observed only when IGF II is included in the patch pipette, indicating direct regulation of the channel by IGF II. We suggest that IGF II stimulates calcium influx by opening this cation channel and that IGF II activates the channel in a unique cell cycle-dependent manner.

Animals↗
PubMed1988

Two types of calcium channels and hormone release in human pituitary tumor cells.

Voltage-gated Ca2+ channel currents were examined in human growth hormone-producing cells using the whole cell variation of patch electrode voltage clamp. In 20 mM Ba2+, Na+-free medium, the inward current was composed of a fast-inactivating component (transient type) and a steady component (long-lasting type). These two types had different properties. The transient type inactivated with the depolarizing prepulse but the long-lasting type did not. The transient type was activated at more negative potential levels than the long-lasting type. Deactivation kinetics of the transient type were slower than that of the long-lasting type. Nitrendipine inhibited and Bay K 8644 enhanced Ca2+ channel currents, and the effects of these agents were more prominent on the long-lasting type than on the transient type. Hormone release was inhibited by nitrendipine and enhanced by Bay K 8644, indicating involvement of Ca2+ influx through voltage-gated channels in the release process.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗