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Biomedical subjects

T Ogiwara

Publications and source records attributed to T Ogiwara.

At least 37 records · Page 2Linked to original sources
PubMed1996

Characterization of pituitary adenylate cyclase-activating polypeptide 38 (PACAP38)-, PACAP27-, and vasoactive intestinal peptide-stimulated responses in N1E-115 neuroblastoma cells.

In this study, the effects of three related peptides, pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), PACAP27, and vasoactive intestinal peptide (VIP), on cyclic AMP (cAMP) accumulation and intracellular Ca2+ concentration ([Ca2+]i) were compared in N1E-115 cells. PACAP38 and PACAP27 stimulated cAMP accumulation up to 60-fold with EC50 values of 0.54 and 0.067 nM, respectively. The effect of VIP on cAMP accumulation was less potent. The binding of 125I-PACAP27 to intact cells was inhibited by PACAP38 and PACAP27 (IC50 values of 0.44 and 0.55 nM, respectively) but not by VIP. In fura-2-loaded cells, both PACAP38 and PACAP27 increased [Ca2+]i with EC50 values around 10 nM. The interactions of these three peptides with ionomycin, a Ca2+ ionophore, and 4 beta-phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, were also determined. Ionomycin increased the cAMP accumulation caused by all three peptides. With low concentrations of PACAP38 or PACAP27, the effect of PMA was inhibitory, whereas at higher concentrations of PACAP (> 1 nM), the effect of PMA was stimulatory. Similar to other agents that elevate cAMP, PACAP38 was an effective stimulator of neurite outgrowth. These results show that (a) PACAP27 and PACAP38 stimulate cAMP accumulation and increase [Ca2+]i through the type I PACAP receptors in N1E-115 cells, (b) ionomycin enhances cAMP accumulation by all three peptides, and (c) activation of protein kinase C has a dose-dependent stimulatory or inhibitory effect on the PACAP38- or PACAP27-stimulated cAMP accumulation.

Calcium↗
PubMed1996

PACAP modulates L-type Ca2+ channel currents in vascular smooth muscle cells: involvement of PKC and PKA.

The effect of pituitary adenylate cyclase activating polypeptide (PACAP) on the L-type Ca2+ channel current (L-channel current) was studied in smooth muscle cells prepared from the rat tail artery. PACAP caused an increase in the amplitude of the L-channel current. The maximal increase (56%) occurred at a PACAP concentration of 1 x 10(-8) M; higher concentrations resulted in a smaller increase. Investigation into the intracellular mechanisms of PACAP action revealed that the increase in L-channel currents was blocked by calphostin C and bisindolylmaleimide IV [protein kinase C (PKC) inhibitors] and mimicked by 4 beta-phorbol 12-myristate 13-acetate (PMA), an activator of PKC. PACAP was also found to cause translocation of PKC, suggesting that the increase in the current by PACAP was due to PKC. In contrast, activation of cAMP-dependent protein kinase (PKA) by 8-bromo-cAMP caused an inhibition of the L-channel current. A high concentration of PACAP (1 x 10(-6) M) had no effect on the L-channel current. The null effect of PACAP on the L-channel current could be converted to an increase by Rp-cAMPs, a cAMP antagonist, and a decrease by calphostin C. PACAP also increased cAMP accumulation. These observations indicate the effect of PACAP on the L-channel current represents the integration of two signaling mechanisms that involve the activation of PKA and PKC.

Animals↗
PubMed1996

Thapsigargin modulates agonist-stimulated cyclic AMP responses through cytosolic calcium-dependent and -independent mechanisms in rat pinealocytes.

The role of mobilization of intracellular Ca2+ in the adrenergic-stimulated cAMP accumulation in rat pinealocytes was investigated with thapsigargin, an agent that inhibits endoplasmic reticulum Ca2+-ATPase. It was found that although thapsigargin alone had no effect on the basal cAMP accumulation, it potentiated the beta-adrenergic-stimulated cAMP response by isoproterenol in a dose-dependent manner. The potentiation was abolished with ethylene glycol bis(beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid-acetoxymethyl ester (EGTA-AM) but persisted in the presence of isobutylmethylxanthine, indicating that thapsigargin enhances cAMP synthesis through elevation of cytosolic intracellular Ca2+ concentration ([Ca2+]i). However, when the pinealocytes were stimulated by norepinephrine, a mixed alpha 1- and beta-adrenergic agonist, thapsigargin dose-dependently inhibited the cAMP response. To investigate this inhibitory effect of thapsigargin, we substituted ionomycin, a [Ca2+]i-elevating agent, and 4 beta-phorbol-12-myristate 13-acetate, an activator of protein kinase C, for the alpha(1)-adrenergic component of the norepinephrine-stimulated response. Although thapsigargin had no effect on the potentiation of the isoproterenol-stimulated cAMP accumulation by ionomycin, it significantly inhibited the potentiation by 4 beta-phorbol-12-myristate 13-acetate. Furthermore, the inhibitory effect of thapsigargin was not affected by cotreatment with EGTA-AM or ionomycin, suggesting that this effect is independent of [Ca2+]i. Similar results were obtained when cyclopiazonic acid was used to inhibit the Ca(2+)-ATPase. Taken together, our results indicate that thapsigargin enhances the beta-adrenergic-stimulated cAMP accumulation through its action in elevating [Ca2+]i but inhibits the potentiation of the beta-adrenergic-stimulated cAMP response by protein kinase C, as a consequence of Ca(2+)-ATPase inhibition.

Animals↗
PubMed1995

Cyclic GMP stimulates growth hormone release in rat anterior pituitary cells.

In this study, the role of cGMP on growth hormone (GH) release was examined using a static monolayer culture prepared from dispersed rat anterior pituitary cells. Treatment with 8-bromo-cGMP (1 microM to 1 mM) stimulated GH release up to 3.8-fold in a concentration-dependent manner. Elevating cGMP with nitroprusside or the C-type natriuretic peptide was also effective in stimulating GH release. The increase in GH release by cGMP-elevating agents occurred without a concomitant increase in cAMP. Unlike cAMP which increased intracellular Ca2+ concentration, 8-bromo-cGMP caused a small reduction in intracellular Ca2+ concentration. Taken together, these results indicate that i) cGMP appears to be another mechanism that regulates GH release, ii) activation of cytosolic or membranous guanylyl cyclase is equally effective in stimulating GH release; and iii) the cGMP-induced GH release appears to be through a mechanism distinct from that of cAMP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Tyrosine kinase inhibitors enhance cGMP production in rat pinealocytes.

The role of tyrosine kinase(s) in the regulation of cGMP accumulation in rat pinealocytes was investigated using three tyrosine kinase inhibitors. Treatment with genistein, erbstatin or the active analogues of tyrphostin selectively increased basal cGMP accumulation in a dose-dependent manner without a concomitant increase in cAMP. In contrast to the norepinephrine- and vasoactive intestinal peptide-stimulated cGMP responses, the stimulatory effect of genistein was not blocked by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine. Furthermore, in the presence of isobutylmethylxanthine, a phosphodiesterase inhibitor, neither genistein nor erbstatin had an effect on cGMP accumulation. These results indicate that tyrosine kinase inhibitors increase pineal cGMP accumulation through inhibition of the metabolism of cGMP.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Potentiation of agonist-stimulated cyclic AMP accumulation by tyrosine kinase inhibitors in rat pinealocytes.

To study cross-talk mechanisms in rat pinealocytes, the role of tyrosine kinase or kinases in the regulation of adrenergic-stimulated cyclic AMP production was investigated. Both norepinephrine- and isoproterenol-stimulated cyclic AMP accumulation were increased by two distinct tyrosine kinase inhibitors, genistein or erbstatin, in a concentration-dependent manner. A similar increase was observed with two other inhibitors, tyrphostin B44 and herbimycin. In contrast, daidzein, an inactive analogue of genistein, was ineffective; whereas vanadate, a phosphotyrosine phosphatase inhibitor, reduced the adrenergic-stimulated cyclic AMP accumulation. The tyrosine kinase inhibitors were effective in potentiating the cholera toxin-or forskolin-stimulated cyclic AMP accumulation, indicating that their sites of action are at the postreceptor level. Neither an activator nor inhibitors of protein kinase C influenced the potentiation of the cyclic AMP responses by genistein, suggesting that the potentiation effect by tyrosine kinase inhibitors does not involve the phospholipase C/protein kinase C pathway. However, when the phosphodiesterase was inhibited by isobutylmethylxanthine, genistein failed to potentiate and vanadate did not inhibit the adrenergic-stimulated cyclic AMP accumulation, indicating that the phosphodiesterase is a probable site of action for these inhibitors. These results suggest that cyclic AMP metabolism in the pinealocytes is tonically inhibited by tyrosine kinase acting on the cyclic AMP phosphodiesterase.

Animals↗
PubMed1993

A study of the judging the anteroposterior mandibular position by gripping the temporal muscle region.

Greene proposed a method for judging the suitability of the mandibular position from the bulging of the temporal muscle. Using his method, we studied the effect of anteroposterior alteration of mandibular position on the building of this muscle. In the temporal muscle, the area suitable for gripping to check mandibular position was, anteroposteriorly, the point 3/5 of the length between the upper margin of the external auditory meatus and the point of intersection of the Frankfort plane and the line perpendicular to it which was drawn from the outer canthus. Vertically, it was approximately at the point 3/5 of the distance from the bottom of the line from the Frankfort plane to the upper edge of the temporal muscle. In patients whose anteroposterior changes in the tapping point were small, anteroposterior changes of 0.2 mm in mandibular position could be detected. However, in patients who had large anteroposterior changes in the tapping point, anteroposterior changes of 0.5 mm in mandibular position could not be verified.

Dental Occlusion, Centric↗
PubMed1992

Thyroid hormone affects the hydrolysis of inositol phospholipids in the rat hypothalamus.

We have attempted to elucidate the effect of thyroid hormone on phospholipase C-linked inositol phospholipid hydrolysis in the rat hypothalamus. Hypothalamic slices of each animal, euthyroid control, hypothyroid, and thyroxine (T4)-supplemented hypothyroid rats were labeled with [3H]myoinositol in the presence of 5 mM LiCl, and then incubated for 60 min in KHG buffer containing either vehicle or 1 mM ouabain, a Na-K ATPase inhibitor. Hypothyroidism caused a significant increase in both basal and ouabain-stimulated accumulation of [3H]inositol phosphate ([3H]IP) in hypothalamic slices, whereas supplement with T4 to hypothyroid rats resulted in a complete restoration of hypothalamic [3H]IP formation to the value of euthyroid control. The present results indicate that thyroid hormone affects phospholipase C-linked inositol phospholipid hydrolysis in the hypothalamus, suggesting that negative feedback action of thyroid hormone may occur at a post-receptor site in the hypothalamus.

Animals↗
PubMed1992

Inhibitory effects of okadaic acid on thyrotropin and prolactin secretion from rat anterior pituitaries.

The present study was undertaken to elucidate the effects of okadaic acid, a potent inhibitor of protein phosphatases, on thyrotropin (TSH) and prolactin (PRL) secretion, and on the hydrolysis of inositol phospholipids in rat anterior pituitaries. Preincubation of anterior pituitaries with okadaic acid caused a dose dependent decrease in TRH- and K(+)-induced TSH secretion, whereas basal secretion of TSH was not affected by pretreatment with okadaic acid. In contrast, okadaic acid resulted in a marked inhibition in both basal, and TRH- and K(+)-stimulated PRL release from anterior pituitaries. In addition, pretreatment with okadaic acid caused a slight, but significant decrease in the formation of [3H]inositol phosphate ([3H]IP) in rat anterior pituitaries. The present study suggests that okadaic acid blocks the release of TSH and PRL by inhibiting Ca2+ influx and that inhibitory effects of okadaic acid on PRL release are, at least in part, due to the inhibition of inositol phospholipid hydrolysis.

Animals↗
PubMed1992

Thyroid hormones regulate the formation of inositol phosphate in response to thyrotropin-releasing hormone in rat anterior pituitaries.

The effects of thyroid hormones on TSH secretion and inositol phospholipid hydrolysis in response to thyrotropin-releasing hormone (TRH) in rat anterior pituitaries were examined. Experimental hypothyroidism caused a significant increase in [3H]inositol phosphate ([3H]IP) formation in response to TRH in rat anterior pituitaries with a concomitant elevation of blood TSH. In contrast, administration of thyroxine (T4) to hypothyroid rats resulted in a complete restoration of blood TSH and TRH-stimulated [3H]IP formation to the euthyroid control value. Furthermore, in vitro pre-treatment of anterior pituitaries with triiodothyronine (T3) produced a dose-dependent decrease in both TSH secretion and the formation of [3H]IP in response to TRH. These results indicate that thyroid hormones regulate TRH receptor-linked inositol phospholipid hydrolysis in the rat anterior pituitary, suggesting that negative feedback action of thyroid hormone occurs at post receptor event in the rat anterior pituitary, which may, to a certain extent, be responsible for the underlying mechanism of T3 inhibition of TSH secretion.

Animals↗
PubMed1992

[Studies on the efficacy and safety of panipenem/betamipron in infections in surgical domain and the safety when mixed with lactate containing infusion].

Studies were done on the effectiveness and safety of panipenem/betamipron, a new carbapenem antibiotic, in infections in the surgical domain and its safety when dissolved in infusions containing lactate. The obtained results are summarized as follows. The preparation, 0.5 g/0.5 g or 1.0 g/1.0 g, was administered by intravenous drip infusion 2 to 3 times a day to 31 cases of patients with infections in the surgical domain. A physiological saline solution was used as the solvent in 21 cases (group A) of them and Solita T3, an infusion containing lactate, was used as the solvent in the 10 remaining cases (group B). As for its clinical effects, results were rated as "excellent" in 20, "good" in 7, "fair" in 3 and "no response" in 1 out of the 31 cases, and the efficacy rate was 87.1%. Regarding its bacteriological effects, results were rated as "disappeared" in 22, "decreased" in 2, "unchanged" in 1 and "unknown" in 1 out of 26 cases from which bacteria were isolated, hence the bacteria-clearance rate was 88.0%. As for side effects, skin rash was seen in 1 case and slight increases of GOT and GPT were noted as abnormal changes in laboratory data in 2 cases. These side effects were all observed among the cases in group A but not at all in group B where a lactate containing infusion was used as the solvent.

Adolescent↗
PubMed1985

Long-term observation of passive Heymann nephritis.

Chronic renal lesion with membranous changes and massive proteinuria similar to human membranous nephropathy was induced in rats through repeated intravenous injections of gamma-globulin fraction of rabbit anti-rat F X 1A antisera (GRAFA) 0.37-1.5 mg/100 g body weight. The injections were administered every 2 or 3 days over a 68-day period for a total of 26 times. It is suggested that a sufficient amount of GRAFA was given to the rats to induce renal lesion, judging from the result that no remarkable differences were observed between the severity of the histopathological and clinical changes in each rat given the various doses of GRAFA. Furthermore, this renal lesion is considered to correspond to human membranous nephropathy morphologically and clinically, judging from the fact that the protein excretion was kept at a plateau, and the capillary lumen was kept almost intact with advanced membranous changes.

Animals↗
PubMed1982

[Experience with high-dose methotrexate therapy for malignant solid tumors].

Thirteen patients with malignant solid tumors, mainly osteogenic sarcomas, were treated by high-dose MTX therapy, 50-400 mg/kg, in a total of 72 cycles. It has been proved that this therapy was relatively safe provided careful clinical surveillance were assured. Of 8 patients with osteogenic sarcomas, 6 had no metastatic lesions on the chest X-rays before this therapy: three were alive without any evidence of disease for 18-25 months after high-dose MTX therapy. In some cases of other malignant solid tumors, particularly intracranial tumors, clinical efficacy was observed. Dose-time relationships, etc. should further be studied for more therapeutic efficacies of high-dose MTX therapy.

Adolescent↗