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Biomedical subjects

A Baba

Publications and source records attributed to A Baba.

At least 91 records · Page 5Linked to original sources
PubMed1998

Isoform-specific alterations in cardiac and erythrocyte Na+,K+-ATPase activity induced by norepinephrine.

BACKGROUND: Myocardial Na+,K+-ATPase activities are decreased in congestive heart failure because of an increase in plasma norepinephrine levels, but it is difficult to monitor the activities in the clinical setting. METHODS AND RESULTS: This study investigated whether erythrocyte Na+,K+-ATPase activity can reflect myocardial enzyme activity and whether isoform-specific alterations occur in the presence of catecholamine. Na+,K+-ATPase activity was measured by the colorimetric method by using the left ventricular myocardium and erythrocytes prepared from eight rabbits given norepinephrine for 7 days and from eight control rabbits that received saline. The protein levels of total catalytic subunit and alpha1- or alpha3-isoform of Na+,K+-ATPase were determined by Western blot analysis. Na+,K+-ATPase activity was lower in both myocardium and erythrocytes from norepinephrine-treated rabbits than control rabbits (P < .01 and P < .01, respectively). There was a close correlation in Na+,K+-ATPase activity between myocardium and erythrocytes (r = .963). Total catalytic subunit protein level was lower in myocardium from norepinephrine-treated rabbits than control rabbits, but the alpha1-isoform level was similar between the two groups. The alpha3-isoform level was lower in norepinephrine-treated rabbits than control rabbits. In erythrocytes, alpha1-isoform was lower in norepinephrine-treated rabbits than control rabbits. CONCLUSIONS: Na+,K+-ATPase activity in myocardium could be reflected in erythrocyte membrane, although there was a difference in isoform-specific regulation between the two.

Animals↗
PubMed1998

Involvement of calcineurin in Ca2+ paradox-like injury of cultured rat astrocytes.

The Ca2+/calmodulin-dependent phosphatase calcineurin may have physiological and pathological roles in neurons, but little is known about the roles of the enzyme in glial cells. We have previously reported that reperfusion of cultured astrocytes in Ca2+-containing medium after exposure to Ca2+-free medium caused Ca2+ influx followed by delayed cell death. In this study, we examined if calcineurin is involved in this Ca2+-mediated astrocytic injury. FK506, an inhibitor of calcineurin, protected cultured rat astrocytes against paradoxical Ca2+ challenge-induced injury in a dose-dependent manner (10(-10)-10(-8) M). Cyclosporin A at 1 microM mimicked the effect of FK506. Rapamycin (1 microM) did not affect astrocyte injury, but it blocked the protective effect of FK506. Deltamethrin (20 nM), another calcineurin inhibitor, had a similar protective effect, whereas okadaic acid did not. FK506 affected neither paradoxical Ca2+ challenge-induced increase in cytosolic Ca2+ level nor Na+-Ca2+ exchange activity in the cells, suggesting that the calcineurin is involved in processes downstream of increased cytosolic Ca2+ level. Immunochemical studies showed that both calcineurin A (probably the A beta2 isoform) and B subunits were expressed in the cells. It is concluded that calcineurin is present in cultured astrocytes and it has a pathological role in the cells.

Animals↗
PubMed1998

Hypogammaglobulinemia during antipsychotic therapy.

Hypogammaglobulinemia in a 22-year-old woman with brief psychotic disorder developed during antipsychotic therapy. Severe decreases in immunoglobulin IgM, IgG, and IgA concentration in serum were observed 4 months after the treatment with chlorpromazine (CPZ) and the other types of antipsychotics. Neither physical diseases nor family history for immunological disturbances was seen. No clinical symptoms in relation to immunological disturbances (i.e. infectious disease), were noted. Gammaglobulin levels in serum returned to a normal range after a replacement of chlorpromazine to timiperone. The hypogammaglobulinemia in the present case was considered to be due to the inhibition of gammaglobulin synthesis by CPZ.

Adult↗
PubMed1998

Studies on disease-modifying antirheumatic drugs. II. Synthesis and activity of the metabolites of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quino line-3-carboxylate (TAK-603).

The metabolites of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmeth yl)quinoline -3-carboxylate (1, TAK-603), which is under clinical evaluation as a new type of disease-modifying antirheumatic drug (DMARD), were prepared to confirm their structures and to study their pharmacological properties. Of the metabolites identified, the 4-(4-hydroxy-3-methoxyphenyl) derivative (2c, M-I) was found to have an anti-inflammatory effect in an adjuvant arthritic rat model, although its potency in this model was slightly lower than that of the parent compound.

Animals↗
PubMed1998

Baroreceptor sensitivity during the compensatory phase of left ventricular overloading.

This study focused on the role of the baroreceptor-mediated control during the compensatory process after acute left ventricular overloading induced by aortic regurgitation (AR). Baroreceptor-heart rate sensitivity was measured using a phenylephrine-induced increase in blood pressure according to the steady state method before, 1 day, 1 week and 4 weeks after production of AR in 7 rabbits, and compared with 6 other rabbits that underwent a sham operation. Blood pressure was monitored noninvasively using Finapres in the unanesthetized state. Four weeks after the procedure, the left ventricular diameters of both end-diastole and end-systole were larger in the rabbits with AR than in the sham-operated rabbits. There was no difference in the left ventricular end-diastolic pressure or cardiac output. Left ventricular weight was higher in the rabbits with AR than in the sham-operated rabbits. Myocardial beta-adrenergic receptor density and norepinephrine content were comparable between the two groups. Baroreceptor-heart rate sensitivity significantly decreased 1 week after production of AR, and this alteration in sensitivity was partially restored 4 weeks after production of AR. These findings suggested that the altered baroreceptor-heart rate sensitivity was reversible, relating to the compensatory process after acute left ventricular overloading, and that these changes had some role in its pathophysiology.

Adrenergic alpha-Agonists↗
PubMed1998

[Response of Na+/Ca2+ antiporter to ischemia and glial/neuronal death].

Brain ischemia produces morphologic and biochemical alterations in astrocytes. This mini-review summarizes astrocytic responses to brain ischemia including our studies on the neuronal and astrocytic Na(+)-Ca2+ exchanger (NCX). NCX is considered to cause Ca2+ efflux (forward mode) or Ca2+ influx (reverse mode), depending on the electrochemical gradient of Na+ across the plasma membranes and membrane potential. We demonstrated that NCX is present in cultured neurons and astrocytes and that there are differences in their properties and distribution ratio of the isoforms between neurons and astrocytes. We also found that Ca2+ depletion followed by reperfusion with Ca(2+)-containing medium caused cell death in cultured astrocytes (Ca2+ paradox-like injury), but not in neurons. The study, carried out by the use of a specific antisense oligomer, provides direct evidence that Ca2+ paradox-like injury is mediated by NCX in the reverse mode. The injury was attenuated by inhibitors of the Na(+)-Ca2+ exchanger, heat shock protein and the calcineurin inhibitor FK506. In a preliminary experiment, we found that brain ischemia decreases the mRNA level of NCX in the hippocampus. Further studies on activation and cell injury of astrocytes will contribute to development of new drugs that modulate the function of astrocytes.

Animals↗
PubMed1998

[Apoptosis of astroglial cells].

Astrocytes, the most abundant glial cell type in the brain, are considered to have physiological and pathological roles in neuronal activities. We found that reperfusion of cultured astrocytes after Ca2+ depletion causes delayed cell death and that the Na(+)-Ca2+ exchanger in the reverse mode is responsible for this Ca(2+)-mediated cell injury (Ca2+ paradox injury). The Ca2+ paradox injury of cultured astrocytes is considered to be an in vitro model of ischemia/reperfusion injury, since a similar paradoxical change in extracellular Ca2+ concentration is reported in ischemic brain tissue. Furthermore, we demonstrated that heat shock proteins, glutathione and calcineurin inhibitors protected astrocytes against Ca2+ paradox-induced cell toxicity. We also observed DNA fragmentation, a typical apoptotic ladder, 2-3 days after hydrogen peroxide exposure. In addition, laser microscopic observation showed that reperfusion after the exposure to hydrogen peroxide caused nuclear condensation of astrocytes. Hydrogen peroxide-induced cell injury and DNA fragmentation were attenuated by the NF-kappa B inhibitor ammonium pyrrolidinedithiocarbamate, 1,10-phenanthroline and a caspase 3 inhibitor. These findings suggest that astrocytes are one of the targets for ROS and the oxidative stress-induced delayed death of astrocytes is at least due to apoptosis.

Animals↗
PubMed1997

Distribution of mRNAs for pituitary adenylate cyclase-activating polypeptide (PACAP), PACAP receptor, vasoactive intestinal polypeptide (VIP), and VIP receptors in the rat superior cervical ganglion.

The distribution of mRNAs for pituitary adenylate cyclase-activating polypeptide (PACAP), PACAP receptor (PACAP-R), vasoactive intestinal polypeptide (VIP) and two subtypes of VIP receptors (VIP1-R and VIP2-R) was examined by in situ hybridization in the superior cervical ganglion (SCG) of the adult rat. PACAP-R mRNA was expressed intensely in virtually all principal neurons. PACAP mRNA was expressed in approximately half of the principal neurons, where the levels of expression vary extensively. Intense expression of VIP mRNA was observed only in a few principal neurons. Neither VIP1-R mRNA nor VIP2-R mRNA was detected in SCG cells. These findings suggest that PACAP, but not VIP, may function as a paracrine or autocrine regulatory factor through PACAP-R in the principal neurons of the SCG.

Animals↗
PubMed1997

Induction of glutamine synthetase by L-alpha-aminoadipate in developmental stages of cultured astrocytes.

Effect of L-alpha-aminoadipate (L alpha AA), a gliotoxic L-glutamate analogue, on glutamine synthetase (GS) activity of rat cultured astrocytes was examined, L alpha AA at sub-toxic concentrations (less than 0.5 mM, for 48 h) increased GS activity of cultured astrocytes. This increase was prevented by 10 microM cycloheximide, an inhibitor of protein synthesis. L alpha AA increased GS activities of astrocytes cultured in three different conditions, i.e. 12-day-old, 5-233k-old and dibutyryl cAMP(DBcAMP)-induced differentiated cultures. Insulin (10 micrograms/ml) and hydrocortisone (10 microM) increased GS activity of 12-day-old cultured cells, but not that of 5-weeks-old and DBcAMP-treated cells. The increase in GS activity was observed after a transient treatment with L alpha AA for 4 h. These results show that the induction of GS by L alpha AA is not related to developmental stages of astrocytes in culture.

2-Aminoadipic Acid↗
PubMed1997

Effect of methamphetamine and dopamine receptor antagonists on cholecystokininlike immunoreactivity in the rat medial prefrontal cortex.

A single intraperitoneal administration of methamphetamine (MAP) reduces cholecystokininlike immunoreactivity (CCK-LI) in medial prefrontal cortex (mPFC) of the rat brain. This report examines the effects of various dopamine (DA) receptor antagonists [haloperidol (HAL), sulpiride (SUL), YM09151-2 (YM), and SCH23390 (SCH)] on MAP-induced abnormal behaviors and the changes of CCK-LI in the rat mPFC. A single subcutaneous administration of HAL (0.25 mg/kg), YM (0.1 mg/kg), or SUL (250 mg/kg) significantly reduced the basal CCK-LI in mPFC by 20-40%; a selective D1 antagonist, SCH (up to 1.0 mg/kg), had no effect on basal CCK-LI. However, the reduction of CCK-LI induced by MAP (20-40%) was abolished by the pretreatment with HAL (0.025 and 0.25 mg/kg), YM (0.01 and 0.1 mg/kg), or SCH (1.0 mg/kg), without being affected by SUL (up to 250 mg/kg). This effect of DA antagonists on MAP-induced change in CCK-LI was associated with an inhibition of MAP-induced stereotyped behaviors. These data suggest that the CCK-containing neurons in rat mPFC are functionally related to the mesocortical DA system and may participate in a development of abnormal behaviors induced by MAP.

Animals↗
PubMed1997

Isoform-specific up-regulation by ouabain of Na+,K+-ATPase in cultured rat astrocytes.

There are two alpha-subunit isoforms (alpha1 and alpha2) and two beta-subunit isoforms (beta1 and beta2) of Na+,K+-ATPase in astrocytes, but the functional heterodimer composition is not known. Ouabain (0.5-1.0 mM) increased the levels of alpha1 and beta1 mRNAs, whereas it decreased those of alpha2 and beta2 mRNAs in cultured rat astrocytes. The increases in alpha1 and beta1 mRNAs were observed at 6-48 h after addition of the inhibitor. Immunochemical analyses showed that ouabain increased alpha1 and beta1, but not alpha2 and beta2, proteins, and that the isoforms in control and ouabain-treated cultures were of glial origin. Low extracellular K+ and monensin (20 microM) mimicked the effect of ouabain on alpha1 mRNA. The ouabain-induced increase in alpha1 mRNA was blocked by the protein synthesis inhibitor cycloheximide (10 microM), the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (30 microM), and the calcineurin inhibitor FK506 (1 nM). These findings indicate that chronic inhibition of Na+,K+-ATPase up-regulates the alpha1 and beta1, but not alpha2 and beta2, isoforms in astrocytes, suggesting a functional coupling of alpha1beta1 complex. They also suggest that intracellular Na+, Ca2+, and calcineurin may be involved in ouabain-induced up-regulation of the enzyme in astrocytes.

Animals↗
PubMed1997

Effect of taurine on angiotensin II-induced hypertrophy of neonatal rat cardiac cells.

The effect of taurine on angiotensin II-induced hypertrophy of cultured neonatal rat heart cells (myocytes and nonmyocytes) was examined. Angiotensin II (1-100 nM) alone caused an increase in the rate of protein synthesis of myocytes without changing the rate of DNA synthesis and cell number. It mediated increases in DNA synthesis and cell number in nonmyocytes. Furthermore, at the lower concentration of 1 nM, it induced c-fos and c-jun expression in both cultured myocytes and nonmyocytes. Exposure of the cells to taurine (20 mM) in the absence of angiotensin II had no effect on either hyperplastic growth or immediate early response gene expression by the two types of cultured cardiac cells. However, myocytes pretreated for 24 h with 20 mM taurine exhibited reduced responsiveness to angiotensin II (1 nM), resulting in lower levels of angiotensin II-mediated stimulation in protein synthesis, and immediate early response gene expression was attenuated. Similarly, taurine treatment of nonmyocytes reduced the degree of hyperplastic growth (DNA synthesis and cell number) and immediate early response gene expression stimulated by angiotensin II. Finally, taurine partially prevented the increase in intracellular free calcium [Ca2+]i mediated by angiotensin II in cardiac cells. Our results indicate that taurine is an effective inhibitor of angiotensin II action.

Angiotensin II↗
PubMed1997

Endothelins promote the activation of astrocytes in rat neostriatum through ET(B) receptors.

The effects of endothelin (ET)-3 and an ET(B) receptor agonist on astrocytic activation in rat caudate putamen were examined by an immunohistochemical staining of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes. A single injection of 40 pmol ET-3 into rat caudate putamen increased the number of GFAP positive cells compared to that in the contralateral saline-injected side. Ala(1,3,11,15)-ET-1 (40 pmol), an ET(B) receptor agonist, also increased the number of striatal GFAP positive cells. The increases in GFAP positive cells were maximum (about 150% of the control side) in 1-2 weeks after injections of the ETs, and then reduced in 4 weeks. A continuous infusion of BQ788, an ET(B) receptor antagonist (23 nmol/day), into the lateral ventricle of the cerebrum antagonized the effect of Ala(1,3,11,15)-ET-1, while BQ788 also reduced the number of GFAP positive cells in saline-injected caudate putamen. Intrastriatal injection of 40 pmol Ala(1,3,11,15)-ET-1 did not affect the number of cells stained by B4 isolectin from Griffonia simplicifolia, which labels activated microglia/macrophages. Intraperitoneal administration of 5 mg/kg per day chloroquine and 0.2 mg/kg per day colchicine did not affect the action of Ala(1,3,11,15)-ET-1. These results suggest that activation of ET(B) receptors is involved in the induction of reactive astrocytes.

Animals↗
PubMed1997

Vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide receptor chimeras reveal domains that determine specificity of vasoactive intestinal polypeptide binding and activation.

Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are closely related G protein-coupled receptors with seven-transmembrane domains. The VIP receptor can bind both VIP and PACAP with high affinity, whereas the PACAP receptor binds only PACAP with high affinity. To elucidate the structural domains involved in a selectivity for VIP binding and the subsequent receptor activation, a series of chimeric receptors between the VIP and PACAP receptors was constructed, expressed in COS-7 cells, and analyzed for ligand binding and cAMP generation. All chimeric constructs bound PACAP with high affinity and subsequently activated cAMP generation similarly to the wild-type receptors. In contrast, profound differences were observed in the potencies of VIP for competition of 125I-labeled PACAP binding to both wild-type receptors and the chimeric receptors. The cAMP responses of these receptors generally correlated with the ability of VIP to compete for PACAP radioligand binding with the exceptions for some particular chimeras. In this report we demonstrate that several domains, including the amino-terminal extracellular domain, the transmembrane domains I and II, and the first extracellular loop of the VIP receptor, are important for the selectivity for VIP binding and responsiveness to VIP. We further show that the third extracellular loop and its proximal domains of the VIP receptor appear to be involved in the VIP recognition, especially the receptor activation process. On the other hand, the direct binding experiments of the VIP radioligand demonstrated that both wild-type receptors and all chimeric receptors have a high affinity binding site for VIP, although this high affinity VIP binding resulted in a biological response only in the VIP receptor or VIP receptor-like chimeras. This suggests that there is a nonbiologically relevant high affinity VIP-binding site within the rat PACAP receptor.

Amino Acid Sequence↗
PubMed1997

Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, activates the JAK/STAT pathway in rat cardiomyocytes.

Leukemia inhibitory factor (LIF) is a member of the interleukin-6 family of cytokines, which induces a wide range of responses in a variety of cells. The aim of this study was to investigate whether LIF induces cardiomyocyte hypertrophy and transmits signals through the JAK/STAT (indicating just another kinase/signal transducer and activator of transcription) pathway in primary cultured neonatal rat cardiomyocytes. LIF increased protein content and [3H]phenylalanine uptake in cardiomyocytes in a dose-dependent manner. LIF (10(3) U/mL) induced rapid tyrosine phosphorylation of gp130, JAK1, JAK2, STAT1, and STAT3 but not Tyk2 or STAT2. LIF also induced autokinase activity of JAK1 in a time-dependent manner. Gel shift assays for interferon gamma activation site/interferon-stimulated responsive element and sis-inducible element (SIE) revealed that LIF induced dimerization of STAT1 and STAT3 and formation of sis-inducing factor complexes, which subsequently interacted with SIE in the promoter. Preincubation with anti-STAT1 and anti-STAT3 antibodies inhibited the binding of SIF complexes. In conclusion, LIF induces cardiac hypertrophy and directly stimulates the JAK/STAT pathway in cardiomyocytes.

Animals↗
PubMed1997

Neurotropic pyrimidine heterocyclic compounds. II. Effects of novel neurotropic pyrimidine derivatives on astrocytic morphological differentiation.

Astrocytes play an important role in supporting nerve regeneration after brain injuries. In this study, the effects of novel neurotropic synthesized pyrimidine compounds on astrocytic morphological differentiation were examined. Treatment of protoplasmic cultured astrocytes with 2-piperidino-5,6-dihydro-7-methyl-6-oxo(7 H)pyrrolo[2,3-d]pyrimidine maleate (MS-430) and the related compounds caused astrocytic process formation in 60 min. The morphology of MS-430-treated cells was similar to that of dibutyryl cAMP (DBcAMP)-treated cells. The astrocytic process formation by MS-430 was observed within 60 min and the maximum effect was obtained at the drug concentration of 0.5-1.0 mM. Rhodamine-phalloidin staining showed that astrocytic cytoskeletal actin was reorganized by MS-430 and DBcAMP. MS-430 did not increase cAMP accumulation in cultured astrocytes. These results suggest that the neurotropic pyrimidines induced astrocytic morphological differentiation through a cAMP-independent mechanism.

Animals↗
PubMed1997

A novel method for induction and detection of anaphylactic reaction using the mouse abdominal wall (AW method).

We found that an antigen-specific anaphylaxis was induced by antigen challenge to the abdominal wall, ear auricle, or subcutaneous tissue in mice sensitized 9 days previously with antigen and adjuvant. The anaphylactic reaction was detected by vascular permeability at the injected site 7 minutes after challenge, which was the best time for estimation. A novel method (AW method) for induction and detection of the anaphylactic reaction in mice was established using the abdominal wall as the challenge site. This method could detect the anaphylactic response in mice 1 to 3 weeks after sensitization. The increase in vascular permeability was completely inhibited by administration of diphenhydramine.

Abdominal Muscles↗