Search PubMed⌕ Search

Biomedical subjects

A Baba

Publications and source records attributed to A Baba.

At least 109 records · Page 6Linked to original sources
PubMed1997

Interaction of orally administered 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole (MKC-242) with 5-HT1A receptors in rat brain.

The present study was carried out to clarify whether orally administered 5-{3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-1,3-be nzodioxole (MKC-242), a serotonin1A (5-HT1A)-receptor agonist having potent anxiolytic-like and antidepressant-like effects in animal models, binds to 5-HT1A receptors in rat brain. Quantitative autoradiography showed that orally administered MKC-242 (0.1-0.5 mg/kg) caused a significant decrease in 3[H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) binding in the hippocampus and dorsal raphe nucleus sections. The decrease in the binding by MKC-242 was observed up to 4 hr after administration, and the effective doses were similar to those in its anxiolytic-like effect in the animal models. Repeated treatment of MKC-242 (0.5 mg/kg/day, p.o.) or buspirone (30 mg/kg/day, p.o.) for 2 weeks did not affect [3H]8-OH-DPAT binding in both sections. These results suggest that orally administered MKC-242 at the low doses that do not show 5-HT1A-receptor-mediated in vivo responses such as the hypothermic effect, adrenocortical effect and the decrease in 5-HT turnover passes the blood-brain barrier and subsequently binds to 5-HT1A receptors in rat brain. In addition, they indicate that repeated stimulation of the receptors by the agonists does not affect the number of the binding sites.

5,7-Dihydroxytryptamine↗
PubMed1997

Inhibition by nitric oxide of the uptake of [3H]serotonin into rat brain synaptosomes.

[3H]Serotonin (5-HT) uptake by synaptosomes of rat brain was dose-dependently inhibited by nitric oxide (NO) donors such as sodium nitroprusside (SNP), 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamin e, 3-morpholinosydnonimine and S-nitroso-L-cysteine (NO-CYS). The inhibitory effect was blocked by reduced hemoglobin. The effect was not mimicked by ferrocyanide and ferricyanide. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-bromo cGMP) did not affect [3H]5-HT uptake into rat cortical synaptosomes. The reduced activity of [3H]5-HT uptake into the cortical synaptosomes pretreated with NO-CYS was partially reversed by washing the preparation after the treatment. Kinetic analysis showed that NO-CYS (100 microM) decreased the Vmax value without any change in the Km value. NO-CYS did not affect the specific binding of [3H]paroxetine, a ligand that binds to the 5-HT transporter, in membranes. NO-CYS and SNP, like iodoacetic acid and sodium cyanide, decreased the ATP content in cortical synaptosomes, but the effect on ATP content was not related to that on [3H]5-HT uptake. These findings suggest that NO inhibits reversibly [3H]5-HT uptake into rat brain synaptosomes without affecting the recognition site of the 5-HT transporter in a cGMP-independent manner, and the observed effect is not due to its metabolic effect.

Adenosine Triphosphate↗
PubMed1997

Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor mRNA in the rat adrenal gland: localization by in situ hybridization and identification of splice variants.

The distribution of mRNA for pituitary adenylate cyclase-activating polypeptide receptor (PACAP-R) was examined by in situ hybridization in rat adrenal gland. In the adrenal medulla, PACAP-R mRNA was expressed in almost all chromaffin cells without any significant expression in the cortical region. Using the reverse transcription-polymerase chain reaction, we analyzed the mRNA expression of PACAP-R splice variant forms in the adrenal gland. The predominant forms observed were the variant having a 28-amino acid insert in the third intracellular loop (termed PACAP-R-hop1). As PACAP is localized in the noradrenaline secreting cells of the adrenal chromaffin cells, and stimulates catecholamine release, the present results suggest that PACAP may serve as a paracrine or autocrine regulatory factor for the chromaffin cells through PACAP-R.

Adrenal Glands↗
PubMed1996

Studies on disease-modifying antirheumatic drugs: synthesis of novel quinoline and quinazoline derivatives and their anti-inflammatory effect.

In the course of our study aimed at developing new types of DMARDs (disease-modifying antirheumatic drugs), we found that quinoline derivative 1a had a potent anti-inflammatory effect in an adjuvant arthritis (AA) rat model, starting from the potent bone resorption inhibitors justicidins as the lead compounds. Further modification of 1a was performed, and various quinoline and quinazoline derivatives having a heteroaryl moiety on the alkyl side chain at the 2-position of the skeleton were prepared. These compounds were evaluated for anti-inflammatory effects using the AA rat model. Most of these compounds, especially those having an imidazole or a triazole moiety on the 2-alkyl chain, exhibited a potent effect. Among the compounds synthesized, ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2, 4-triazol-1-yl-methyl)quinoline-3-carboxylate (12d), having an ED50 value of 2.6 mg/kg/day (anti-inflammatory effect in an AA rat model, po), was selected as a candidate for further investigation. In vitro, 12d inhibited mitogen-induced proliferation at 10(-7)-10(-5) M but not prostaglandin E2 production at 10(-5) M. Moreover, 12d preferentially inhibited the IFN-gamma production by Th1-type clones over the IL-4 production by Th2-type clones. This preferential suppression of Th1 cytokine production is considered the essential immunomodulating action of 12d for the present. Synthesis and structure-activity relationships for this novel series of quinoline and quinazoline derivatives are detailed.

Animals↗
PubMed1996

Myocardial sympathetic denervation prevents chamber-specific alteration of beta-adrenergic transmembrane signaling in rabbits with heart failure.

OBJECTIVES: The purpose of this study was to assess the effect of myocardial sympathetic denervation on the chamber-specific alteration of beta-adrenergic signaling in left ventricular failure in rabbits. BACKGROUND: Local abnormalities in sympathetic nerve terminals, including the neuronal reuptake of norepinephrine, are thought to be responsible for the chamber-specific regulation of beta-adrenergic signaling in heart failure. METHODS: Sixteen rabbits were given 6-hydroxydopamine, 25 mg/kg body weight intravenously on days 1 and 2 and 50 mg/kg intravenously on days 7 and 8. Another 16 rabbits received vehicle. Aortic regurgitation was induced in eight of the 6-hydroxydopamine-treated and eight of the vehicle-treated rabbits on day 14. Another eight of the 6-hydroxydopamine-treated and eight of the vehicle-treated rabbits underwent a sham operation. The hearts were excised for biochemical analysis on day 21. RESULTS: Hemodynamic characteristics on day 21 showed left ventricular failure in both the aortic regurgitation groups. The plasma norepinephrine concentration on day 21 was higher in both the aortic regurgitation groups than in the sham groups. The beta-adrenoceptor densities and isoproterenol plus 5'-guanylylimidodiphosphate-, 5'-guanylylimidodiphosphate- and sodium fluoride-stimulated adenylyl cyclase activities were decreased only in the failing left ventricle of the vehicle-pretreated aortic regurgitation group, but in both ventricles of the 6-hydroxydopamine-pretreated aortic regurgitation group. The basal and forskolin-stimulated adenylyl cyclase activities were similar in both the aortic regurgitation groups and in the sham groups. CONCLUSIONS: Sympathetic denervation prevented chamber-specific alterations in beta-adrenergic signaling in acute left ventricular failure. Local loss of sympathetic nerve endings, and especially the defective neuronal norepinephrine reuptake, are likely to be responsible for the chamber-specific alteration of the beta-adrenoceptor-G protein-adenylyl cyclase system in heart failure in rabbits.

Adenylyl Cyclases↗
PubMed1996

Heat shock protects cultured rat astrocytes in a model of reperfusion injury.

We have previously found that incubation of cultured rat astrocytes in Ca(2+)-free medium caused an increase in intracellular Ca2+ ([Ca2+]i) followed by delayed cell death. Here, we examined whether thermal stress protects astrocytes from cell death in this model system of reperfusion injury. Cultured astrocytes were preincubated at 40-44 degrees C for 10-20 min in fetal calf serum-free medium, incubated at 37 degrees C for 24 h in serum-containing medium, and subjected to the in vitro reperfusion experiment. Thermal stress attenuated reperfusion-induced cell toxicity. Furthermore, the stress increased cell viability after incubation with serum-free medium containing Ca2+. These effects of heat shock required incubation in serum-containing medium for at least 12 h after heat shock, and it was blocked by the protein synthesis inhibitor cycloheximide. Thermal stress increased synthesis of several proteins, and one of the inducible proteins was identified as the 72-kDa heat shock protein by an immunoblot analysis. Neither the increase in [Ca2+]i nor the Na(+)-Ca2+ exchange activity in astrocytes induced in this model were affected by thermal stress. These findings suggest that heat shock proteins protect astrocytes from cell death in a model of reperfusion injury and they may affect processes down stream of the increase in [Ca2+]i.

Animals↗
PubMed1996

Autoradiographic study on the pharmacological characteristics of [3H]3-OH-PCP binding sites in rat brain.

The pharmacological characteristics and the regional distribution of [3H]3-OH-PCP (1-[1(3-hydroxyphenyl)-cyclohexyl]piperidine) binding were investigated in rat brain by quantitative autoradiography. Kinetic analysis of [3H]3-OH-PCP binding revealed fast and slow components, in the association and dissociation studies. The regional distribution of binding closely corresponded to those of binding sites labeled by [3H]N-[l-(2-thienyl)-cyclohexyl]3,4-piperidine (TCP) and [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate (MK 801). High densities of [3H]3-OH-PCP binding sites were found in the stratum radiatum and orients of field CA1 in the hippocampus and in the outer layers of cerebral cortices. In contrast, low levels of binding were seen in the brain stem and the granular cell layer of the cerebellum. [3H]3-OH-PCP binding was strongly inhibited by MK 801 and 3-OH-PCP, while the potency of (+)-SKF 10047 in inhibiting [3H]3-OH-PCP binding was less in the cerebral cortex and hippocampus. The antagonists for the glutamate, glycine and polyamine recognition sites at the NMDA/PCP receptor complex displaced [3H]3-OH-PCP binding sites with a potency similar to that of [3H]MK 801. These findings suggest that the [3H]3-OH-PCP binding site is similar or identical to the PCP binding site labeled by [3H]TCP and [3H]MK 801.

Animals↗
PubMed1996

Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: an in situ hybridization study.

The distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide (PACAP) receptor (PACAP-R) was examined in the rat brain, and also in the hypophysis and pineal gland, by in situ hybridization with a specific 35S-labeled riboprobe which was generated from a rat PACAP-R cDNA clone. In the brain, expression of PACAP-R mRNA was most prominent in the periglomerular and granule cells of the olfactory bulb, granule cells of the dentate gyrus, supraoptic nucleus, and area postrema. The expression was also intense in the piriform, cingulate, and retrosplenial cortices, pyramidal cells in CA2, non-pyramidal cells in CA1-CA3, neuronal cells in the hilus of the dentate gyrus, lateral septal nucleus, intercalated amygdaloid nucleus, anterodorsal thalamic nucleus, most of the midline and intralaminar thalamic nuclei, many regions of the hypothalamus, dorsal motor nucleus of the vagus nerve, hypoglossal nucleus, and lateral reticular nucleus. No significant expression was detected in the mitral and tufted cells in the olfactory bulb, pyramidal cells in CA1 and CA3, posterior nuclear group of the thalamus, dorsal lateral geniculate nucleus, and Purkinje, Golgi, and granule cells in the cerebellar cortex. Moderate-to-weak expression was further observed in many other regions of the brain. In the cerebellar cortex, presumed Bergmann glia cells showed moderate expression. In the hypophysis, the expression was moderate in the anterior lobe, and weak to moderate in the posterior lobe; no significant expression was observed in the intermediate lobe. In the pineal gland, the expression was very weak, if any. Thus, the expression of PACAP-R was detected not only on neuronal cells but also on some particular glial cells. The present study has shown, for the first time, the exact site of PACAP-R expression in the brain and hypophysis. Although the functional significance of PACAP and PACAP-R in the brain still remains to be clarified, the present results are considered to provide some direction for future functional studies.

Animals↗
PubMed1996

cDNA cloning of a mouse pituitary adenylate cyclase-activating polypeptide receptor.

A cDNA clone for mouse pituitary adenylate cyclase-activating polypeptide (PACAP) receptor (PACAP-R) was obtained from the brain using reverse transcription-polymerase chain reaction (RT-PCR). The recombinant PACAP receptor expressed in COS cells bound PACAP with about 1000-times higher affinity than vasoactive intestinal polypeptide (VIP), and PACAP stimulated adenylate cyclase through the cloned PACAP receptor. The mouse PACAP receptor consists of 496 amino acids, contains seven transmembrane segments and has 98.4%, 93.0%, and 92.5% identity with the rat, bovine, and human PACAP-R, respectively.

Amino Acid Sequence↗
PubMed1996

Effects of phencyclidine metabolites on serotonin uptake in rat brain.

The effects of phencyclidine (PCP) and its metabolites on serotonin (5-hydroxytryptamine, 5-HT) receptors were studied. PCP and its metabolites inhibited the uptake of [3H]5-HT and the binding of [3H]paroxetine in rat brain, while they failed to inhibit either [3H]5-HT binding to 5-HT1 receptors or [3H]ketanserin binding to 5-HT2 receptors. The trans-isomer of 4-phenyl-4-(I-piperidinyl)cyclo-hexanol (trans-4-PPC), the major metabolite of PCP, rather than PCP itself, inhibited [3H]5-HT uptake most potently. These results suggest that the serotonergic effects of PCP, in part, may be based on the effects of PCP metabolites on 5-HT uptake.

Animals↗
PubMed1996

Expression pattern of messenger RNAs for prostanoid receptors in glial cell cultures.

Expression level of messenger RNAs (mRNAs) for prostanoid EP3, FP, and TP receptors was investigated in cultured rat astrocytes, oligodendrocytes, and microglia, as well as in meningeal fibroblasts, rat glioma C6 cells, rat pheochromocytoma PC12 cells, whole brain, and several peripheral tissues by reverse transcriptase-polymerase chain reaction. Cultured astrocytes and oligodendrocytes expressed mRNAs for 3 prostanoid receptors examined. In contrast, cultured microglia and pheochromocytoma PC12 cells expressed EP3 and TP receptor mRNAs, but not FP receptor mRNA. Glioma C6 cells expressed only TP receptor mRNA among 3 prostanoid receptors with the same expression level as that in astrocytes. Cultured meningeal fibroblasts expressed 3 receptor transcripts, and their expression levels were lower than those in astrocytes. Expression level of mRNA for each prostanoid receptor in cultured glial cells was higher than that in whole brain. These observations suggest that each prostanoid has its specific roles in each glial cell type of the brain.

Animals↗
PubMed1996

Inhibition of vanadate-induced astrocytic stress fiber formation by C3 ADP-ribosyltransferase.

Mechanisms of vanadate-induced actin reorganization were examined in cultured astrocytes. Treatment of protoplasmic astrocytes with 0.5 mM dibutyryl cAMP (DBcAMP) caused the disappearance of stress fibers (SFs) and focal adhesions (FAs) accompanied with cellular stellation. A subsequent addition of 1 mM orthovanadate (VO4(3-) reorganized SFs and FAs in DBcAMP-treated cells. The newly formed FAs had increased phosphotyrosine levels. VO4(3-) reorganized SFs and FAs in stellate astrocytes induced by 5 microM cytochalasin B, 50 microM ML-9 and 20 microM W-7. Cytoplasmic microinjection of 20 micrograms/ml C3 ADP-ribosyltransferase of C. botulinum, which inactivates rho proteins, caused disappearance of SFs. The effect of C3 enzyme on SFs was not reversed by a subsequent addition of VO4(3-). These results suggest that rho proteins are involved in vanadate-induced reorganization of cytoskeletal actin.

ADP Ribose Transferases↗
PubMed1996

Endothelin-induced cytoskeletal actin re-organization in cultured astrocytes: inhibition by C3 ADP-ribosyltransferase.

We investigated signal transduction mechanisms of endothelin (ET) receptor-mediated actin re-organization of rat cultured astrocytes. Staining of filamentous actin (F-actin) showed that stress fibers were a prominent cytoskeletal actin structure in protoplasmic astrocytes. A treatment with 0.5 mM dibutyryl cAMP (DBcAMP) caused cytoplasmic retraction and disappearance of stress fibers of astrocytes. A subsequent addition of 1 nM ET-3 after the DBcAMP treatment expanded the cytoplasm and stimulated stress fiber formation. ET-1, sarafotoxin S6b, and [Ala1,3,11,16]-ET-1 had similar effects. Pre-treatment with 0.1 microgram/ml pertussis toxin (PTX) and chelation of cytosolic Ca2+ did not affect astrocytic stress fiber formation by ET-3. ET-3 stimulated stress fiber formation in stellate astrocytes induced by 50 microM ML-9, 20 microM W-7, and 5 microM cytochalasin B (CB). Cytoplasmic microinjection of C3ADP-ribosyltransferase of C. botulinum (C3 enzyme), which impairs the interaction between rho proteins and the effectors, prevented ET-3-induced stress fiber formation and cytoplasmic expansion in DBcAMP-and CB-treated cells. Effects of ET-1 and sarafotoxin on stress fiber formation were also prevented by C3 enzyme. On the other hand, injection of C3 enzyme did not affect increase in cytoplasmic Ca2+ levels induced by ET-3. These results suggest that rho proteins are involved in the ET receptor-mediated actin re-organization of astrocytes.

ADP Ribose Transferases↗