Characterization of the AT2 receptor on rat ovarian granulosa cells.
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Animals↗
Biomedical subjects
S Usuki
Publications and source records attributed to S Usuki.
Induction of ganglioside biosynthesis and neurite outgrowth of primary cultured neurons by L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol.
We reported previously that stereoisomers of 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), the D-threo and L-threo forms, exerted inhibitory and stimulatory effects on glycosphingolipid (GSL) biosynthesis in B16 melanoma cells, respectively. In the present study, the primary cultured rat neocortical explants were treated with L- or D-threo-PDMP. These isomers exhibited opposite effects on neurite outgrowth: D-PDMP was inhibitory at concentrations ranging from 5 to 20 microM, whereas L-PDMP was stimulatory over the same concentration range, and the maximal effect was observed at 10-15 microM. Rat neocortical explants were doubly labeled with [14C]serine and [3H]galactose at 15 microM L- or D-PDMP. L-PDMP increased the incorporations of both labels into sphinganine, sphingosine, ceramide, sphingomyelin, neutral GSLs, and gangliosides, whereas D-PDMP inhibited the glucosylation of ceramide resulting in a reduction of ganglioside biosynthesis and accumulation of precursors of glucosylceramide, ceramide, and sphingomyelin. To clarify the stimulatory effect of L-PDMP on GSL biosynthesis, serine palmitoyltransferase, sphingosine N-acyltransferase, glucosylceramide synthase, lactosylceramide synthase, GM3 synthase, and GD3 synthase were quantified in cell lysates of explants pretreated with this agent. Serine palmitoyltransferase was fully activated up to 150% of the control. Furthermore, marked increases in the activities of lactosylceramide synthase (200%), GM3 synthase (240%), and GD3 synthase (300%) were observed. These results suggest that the neurotrophic action of L-PDMP may be ascribable to its stimulatory effect on the biosynthesis of GSLs, especially that of gangliosides.
Animals↗
Characterization of angiotensin II receptor type 2 during differentiation and apoptosis of rat ovarian cultured granulosa cells.
We examined the change in the content of angiotensin II (AII) receptor type 2 (AT2) during differentiation and apoptosis of rat ovarian granulosa cells in culture. The AT2 content was not changed by follicle stimulating hormone (FSH), a differentiation factor of granulosa cells, but was markedly increased in FSH-free media. The cells cultured without FSH underwent internucleosomal DNA fragmentation characteristic of apoptosis, which occurs during follicle atresia. AII augmented the increase in the AT2 content in the absence of FSH. This AII-induced augmentation was suppressed by the AT2-selective antagonist PD123319 but not by Dup753, an antagonist specific for type 1 receptor, suggesting that AII up-regulates the AT2 expression via AT2 itself. These data strongly support the hypothesis that AT2 might modulate the onset and progression of follicle atresia involving apoptosis of granulosa cells.
Angiotensin II↗
Stimulation of glycosphingolipid biosynthesis by L-threo-1-phenyl-2-decanoylamino-1-propanol and its homologs in B16 melanoma cells.
Previous studies have demonstrated that the ceramide analog D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-threo-PDMP) inhibits glucosylceramide (GlcCer) synthase and thus leads to extensive depletion of glycosphingolipids (GSLs) biosynthesized from GlcCer [reviewed by Radin, N.S., Shayman, J.A., and Inokuchi, J. (1993) Adv. Lipid Res. 26, 183-213). In the present study, stereospecificity of PDMP activity was demonstrated with an enantiomeric pair, D-threo-PDMP and L-threo-PDMP. Treatment of B16 melanoma cells with the D-threo or L-threo isomer produced contrasting changes of GSL biosynthesis, as monitored by metabolic labeling with [3H]Gal. D-PDMP markedly inhibited incorporation of radioactivity into GlcCer, LacCer, and GM3 as expected, whereas the L-threo isomer significantly increased it. Homologs of L-PDMP having different N-acyl chains were synthesized and also tested for their effects. Among them, the compounds having C8-C14 acyl chains increased incorporation of the radioactivity into GSLs to different degrees, demonstrating that the stimulatory effect of the L-threo homologs depends on acyl chain length. In order to elucidate the biochemical mechanisms of these PDMP effects, the activities of GlcCer synthase, LacCer synthase, and GM3 synthase in B16 cell lysates were measured in the presence of PDMP. D-Threo-PDMP but not the L-threo isomer inhibited both LacCer and GM3 synthases as well as GlcCer synthase, suggesting that the ceramide-like structure of the D-PDMP molecule interacted stereospecifically with these GSL-synthesizing enzymes. On the other hand, L-PDMP had no effect in the in vitro assays.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Case report: thyrotropin-releasing hormone-induced myoclonus and tremor in a patient with Hashimoto's encephalopathy.
The authors investigated the possibility of a thyrotropin-releasing hormone-related mechanism in a 43-year-old Japanese woman with Hashimoto's encephalopathy who experienced three relapses closely associated with the menstrual cycle. Her symptoms began at ovulation, worsened during the luteal phase, and improved during the menstruation phase. No abnormalities were found by brain magnetic resonance imaging and cerebral angiography. Intravenous administration of thyrotropin-releasing hormone induced symptoms of myoclonus and tremor similar to those observed during an exacerbation. The intensity and duration of involuntary movements induced by thyrotropin-releasing hormone were dose-dependent. The patient's symptoms were controlled effectively by thyroxine replacement therapy. On the basis of these findings, thyrotropin-releasing hormone may have an important role in Hashimoto's encephalopathy.
Adult↗
Tokishakuyakusan effect on DNA polymerase alpha activity in relationship to DNA synthesis before and/or after the LH/FSH surge in rats.
DNA polymerase alpha activity in ovaries of mature cycling rats during the normal estrous cycle changed in a cyclic manner with a peak at 1800 h in proestrus. Tokishakuyakusan (TS) in vivo did not affect the changes in DNA polymerase alpha and beta activities during the estrous cycle. LH and FSH at 1000 or 1700 h in proestrus increased DNA polymerase alpha activity, but the DNA polymerase alpha activity induced by LH or FSH was not significantly affected by the addition of TS. DNA polymerase beta activity did not change with LH, FSH or TS. In PMS-treated or -untreated immature rats, TS enhanced ovarian DNA polymerase alpha activity but had no significant effect on LH or FSH action. In ovaries, incubated in vitro, in untreated mature or immature rats, TS enhanced ovarian DNA polymerase alpha activity but had no significant effect on LH or FSH action. These results suggest that TS stimulates ovarian DNA polymerase alpha activity in relationship to DNA synthesis and does not affect the effect of LH or FSH on the activity by preovulatory follicle before and/or after the LH/FSH surge.
Animals↗
Effect of dithiothreitol on angiotensin II receptor type II in rat ovarian cultured granulosa cells.
Dithiothreitol markedly increased the ligand binding affinity of angiotensin II (AII) receptor type II (AT2) without affecting its antagonist selectivity in cultured ovarian granulosa cells, demonstrating that this AT2 is of the dithiothreitol-sensitive type. Dithiothreitol is useful for specifically detecting low levels of the AT2 in the ovary, where it plays roles that are probably related to atresia.
Angiotensin II↗
[Assessment of left ventricular wall motion and myocardial viability in infarcted area by two-dimensional exercise echocardiography in patients with old myocardial infarction].
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Echocardiography↗
Endothelin-renin-angiotensin-atrial natriuretic peptide system in ovaries: an intraovarian ERAANP system.
In a recent investigation of the ovary, high levels of endothelin-1 (ET-1), the renin-angiotensin system (RAS), and atrial natriuretic peptide (ANP) were identified. It was determined that ET, RAS, and ANP, alone or together, affected ovarian function. It is important that mutual relationships of these vasoactive and hormonal peptides, which coexist in the ovary, are examined to determine their in vivo functions. This study, using immature rats treated with pregnant mare's serum gonadotropin (PMS), examined the effects of ET-1, angiotensin II (Ang II) and ANP, individually or in combination, on steroidogenesis by granulosa cells (GCs) cultured for 72 h. ET-1 Ang II, and ANP, alone or combined, also had a mutual effect on steroidogenesis. Concomitantly with previous findings on the ovary, the authors propose that the intraovarian endothelin-renin-angiotensin-ANP system (ERAANPS) functions as a novel intraovarian regulator system.
Angiotensin II↗
[A successful VA bypass treatment in patient with severe pulmonary hypertension].
Report of a case of a patient with pulmonary hypertension associated with pericardial effusion who was treated by VA bypass during life-threatening right ventricular failure. A 63-year-old man was admitted to our hospital complaining of chest pain and dyspnea. Echocardiography revealed the patient had severe pulmonary hypertension and pericardial effusion. Though there were deep Q waves in ECG, his coronary angiography revealed normal coronary arteries. Pulmonary scintigraphy showed no evidence of pulmonary thromboembolism. As he developed hypotension and anuria, emergency pericardial drainage was carried out without any beneficial effect. Because no effective drugs were found to control his systemic hypotension and pulmonary hypertension, he was treated by VA bypass to save his life. Although his systemic pressure rose to normal level following institution of VA bypass, his pulmonary pressure remained high constantly, around 60-70mmHg. The VA bypass was discontinued on the 6th day because of bleeding tendency. 3 months after VA bypass, though he had not been given any drugs to control pulmonary hypertension, his pulmonary arterial pressure dropped down to within normal range. Though the exact mechanism or etiology of pulmonary hypertension remained unclear, this may be a rare case treated by VA bypass successfully for life-threatening right ventricular failure caused by pulmonary hypertension.
Extracorporeal Membrane Oxygenation↗
Regulation of activin beta A mRNA level by cAMP.
We demonstrated the presence of five species of the activin beta A mRNA in human placenta and one major RNA associated with two minor RNAs of the activin in the fetal membrane. We investigated the effect of 8-bromo-cAMP (8-Br-cAMP) on accumulation of activin beta A subunit mRNA in human fibrosarcoma HT1080 cells. Although low levels of the activin mRNA were detectable in the untreated cells, the one main RNA species was predominantly accumulated by 8-Br-cAMP. We propose that generation of multiple activin mRNAs in the fetal membrane and cAMP-treated HT1080 cells is presumably due to a cell-specific alternative polyadenylation.
8-Bromo Cyclic Adenosine Monophosphate↗
High susceptibility of analbuminemic rats to neurogenic tumor induction by transplacental administration of N-ethyl-N-nitrosourea.
The susceptibilities of Nagase analbuminemic rats (NAR) and control Sprague-Dawley rats (SDR) to N-ethyl-N-nitrosourea (ENU) were compared. In Experiment I, the rats were given daily subcutaneous injections of 10 mg/kg of ENU for a week from 4 weeks of age. In Experiment II, mother rats were given a single subcutaneous injection of 60 mg/kg of ENU on day 17 of pregnancy and tumor development in their offspring was examined. In Experiment I, the incidence of neurogenic tumors was slightly, but not significantly, higher in NAR than in control rats. In Experiment II, the incidence of total tumors including neurogenic tumors was significantly higher in NAR (40/43, 93.0%) than in SDR (13/61, 21.3%). NAR showed particularly high susceptibility to induction of neurogenic tumors (34/43, 79.1%) and renal tumors (15/43, 34.9%). In an attempt to elucidate the underlying mechanisms of the increased susceptibility of NAR to ENU, O6-ethylguanine, a major premutagenic ethylated DNA adduct, was quantitated in fetal brain DNA of NAR and SDR after a pulse exposure to 60 mg/kg ENU. No significant difference in the initial formation or subsequent repair of O6-ethylguanine was observed in the two strains, indicating that abnormality at some later stage(s) of chemical carcinogenesis may lead to the increased susceptibility of NAR to induction of neurogenic tumors.
Animals↗
A proposal of ovarian ERAANPS (endothelin-renin-angiotensin-atrial natriuretic peptide system) and effects of tokishakuyakusan, keishibukuryogan, shakuyakukanzoto and unkeito on the ERAANPS.
We have previously shown the presence in a high concentration of endothelin-1 (ET) in the corpus luteum and renin-angiotensin system (RAS) and binding sites for atrial natriuretic peptide (ANP) in the ovarian follicle. The present study was undertaken to identify the existence of ET, renin, angiotensin II and the binding site for ANP in the ovary at proestrus and examine in vivo the effects of herbal medicines [Tokishakuyakusan (TS), Keishibukuryogan (KB), Shakuyakukanzoto (SK) and Unkeito (UT)] on them. ET, all components of RAS and binding sites for ANP were found at high levels in the ovary. TS, KB, SK and UT decreased the ET levels in ovary, while components of RAS and binding sites for ANP have the propensity to increase. However, ET, renin, angiotensin II and ANP levels in plasma were not at all affected before and after treatment with TS, KB, SK or UT. Taken together with previous observations showing the existence of ET, RAS and the binding site for ANP in the ovary, we propose here the ERAANPS (endothelin-renin-angiotensin-ANP system) in the ovary as a functional regulator. Further, these results suggest that TS, KB, SK or UT may regulate the ovarian ERAANPS.
Animals↗
Effects of tokishakuyakusan, keishibukuryogan and unkeito on DNA polymerase alpha activity in uteri of pregnant mare's serum gonadotropin-treated immature rats.
To provide some insights how herbal medicines affect deoxyribonucleic acid (DNA) synthesis in the uterus, the DNA polymerase activities (alpha and beta) in uterine samples taken from rats were measured. DNA polymerase alpha activity with respect to DNA content revealed alpha cyclic change with the highest level on proestrus, while DNA polymerase beta activity showed no significant changes during the estrous cycle. The increased period of the activity coincided with that of 17 beta-estradiol (E2) but not progesterone (P4) in the blood. Injection of 10 IU pregnant mare serum gonadotropin (PMS) on day 27 of age gradually increased DNA polymerase alpha activity in uteri, while concomitant treatment with PMS and 200 micrograms Tokishakuyakusan (TS), Keishibukuryogan (KB) or Unkeito (UT) suppressed the enzyme activity, with a most remarkable effect of KB. These results suggest that TS, KB or UT suppresses in vivo DNA polymerase alpha activity induced by PMS in the rat uterus.
Animals↗
Effects of tokishakuyakusan, keishibukuryogan, shakuyakukanzoto and unkeito on ovarian endothelin, renin and angiotensin II in pregnant mare's serum gonadotropin-treated immature rats.
We have previously proposed the ovarian ERAANPS (endothelin-rein- angiotensin-atrial natriuretic peptide system). The present study was undertaken to examine in vivo the effects of herbal medicines [Tokishakuyakusan (TS), Keishibukuryogan (KB), Shakuyakukanzoto (SK) and Unkeito (UT)] on endothelin-1 (ET), renin and angiotensin II (A II) in the ovaries, of immature rats treated with 10 IU PMS for 48 h. ET and all components of renin-angiotensin system (RAS) were found at high levels in the ovary. Concomitant treatment with PMS plus TS, KB, SK or UT, especially TS and UT, tended to decrease the ET levels in ovary, while components of RAS tended to increase. However, ET, renin and A II levels in plasma were not at all affected after treatment with TS, KB, SK or UT. These results suggest that TS, KB, SK or UT may regulate the ovarian ERAANPS.
Animals↗
Effects of Tokishakuyakusan, Keishibukuryogan and Unkeito on DNA polymerase alpha activity in PMS-treated immature rat uterus incubated in vitro.
We have recently found that Tokishakuyakusan (TS), Keishibukuryogan (KB) or Unkeito (UT) inhibits in vivo DNA polymerase alpha activity in the rat uterus stimulated by PMS. In this study, uteri resected 24 h after injection of PMS on day 27 of age were incubated in vitro with 20 micrograms/ml of extract of TS, KB or UT for 4 h. The DNA polymerase alpha activity in uteri tended to decrease after the addition of TS, KB or UT with significant difference (P < 0.05) compared with TS-, KB- and UT-untreated control groups. These results suggest that TS, KB or UT, especially KB, tends to inhibit directly the enzyme activity in rat uterus.
Animals↗
[Augmentation of left ventricular slow filling in hypertrophic cardiomyopathy].
To investigate the significance of augmentation of left ventricular slow filling, trans-mitral flow (TMF) was echocardiographically observed through pulsed Doppler method in 116 patients with hypertrophic cardiomyopathy (HCM), 74 with dilated cardiomyopathy (DCM), 27 with mitral regurgitation (MR), 86 with old myocardial infarction (OMI) and 80 normal controls (C). The slow filling-wave (SFW) in TMF was defined as the filling wave with obvious peak velocity during slow filling phase. The peak velocities (E, A, S) of the early filling, the atrial contraction and the slow filling waves were measured. The SFW was divided into two patterns according to the S and E ratio: large SFW (S/E greater than or equal to 1/2) and small SFW (S/E less than 1/2). 1) The small SFW was more frequently, but not significantly, observed patients with MR (37%) than in normal subjects (18%), patients with HCM (10%), DCM (4%) and OMI (7%). However large SFW was observed in 16 patients (14%) with HCM, but not in normal subjects and patients with other cardiac diseases excluding one patient with DCM. 2) In normal subjects and patients with DCM, OMI and MR, those with small SFW had larger E and smaller A/E than those without small SFW. However in patients with HCM, there was no difference in these indices (E and A/E) according to whether the patients were with or without SFW. 3) In HCM, patients with large SFW had significantly smaller E and significantly larger isovolumic relaxation time than those without SFW. Thus, appearance of the large slow filling wave, which might be caused by abnormal relaxation of the left ventricle, was frequently observed in patients with HCM.
Adult↗
Endothelin-1 in luteal tissue.
The aim of this study was to immunologically and biologically detect endothelin-1 (ET-1) in rat corpora lutea (CL). Recently, we established a highly sensitive and specific sandwich-enzyme immunoassay (EIA) for ET-1. Using this assay, the presence of ET-1 was investigated in superovulated ovaries, induced with pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG), and ovaries from pseudopregnant rats, induced by cervical stimulation. A high concentration of immunoreactive endothelin-1 (ir-ET-1) was found in the CL. On reverse phase-high performance liquid chromatography (RP-HPLC) coupled with EIA, ir-ET-1 was exclusively eluted at the same position as synthetic ET-1, indicating that ir-ET-1 is identical to ET-1. The level of ir-ET-1 was significantly (P less than 0.001) higher in the CL 7 days after hCG injection than it was 4 days after hCG injection. On day 7 of pseudopregnancy (PSP), the ir-ET-1 level was also significantly (P less than 0.001) higher than on day 4 of PSP. These results demonstrated that ET-1 is present in a high concentration in the CL, suggesting a new intraovarian peptide which may have a physiological function in the ovary and which may vary in quantity according to the age of the CL.
Adsorption↗