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M Hirobe

Publications and source records attributed to M Hirobe.

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

Chronic administration of 1-benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous amine in the brain, induces parkinsonism in a primate.

1-Benzyl-1,2,3,4-tetrahydroisoquinoline hydrochloride (1Bn TIQHCl) (22 mg/kg per day) was subcutaneously injected into a monkey, Macaca fascicularis for 66 days to investigate its acute and chronic effects Parkinsonism like motor symptoms appeared, and the acute toxicity was stronger than the chronic toxicity. This result suggested that 1BnTIQ may induce parkinsonism in humans. 1BnTIQ content in various regions of the monkey brain was determine by the gas chromatography-selected ion-monitoring method, but no significant variation was found.

Animals↗
PubMed1996

Effects of new endogenous nonprotein amino acids, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives, on behavior of mice.

Several 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids were synthesized and found to have a transiently increasing effect on the locomotor activity of mice after peripheral injection. Three of the active compounds were detected in the brain after intraperitoneal administration. Two of them, the 7-hydroxy and 7-hydroxy-6-methoxy derivatives, were found as endogenous compounds in untreated rat brain and may play a physiological role. The effects of some of these compounds on the level of various endogenous amines, amino acids and metabolites were examined.

Amino Acids↗
PubMed1996

Singlet oxygen (1 delta g) generation from coproporphyrin in Propionibacterium acnes on irradiation.

Although singlet oxygen has been postulated to be a highly reactive and toxic intermediate, there has been no evidence of considerable generation of singlet oxygen in vivo level except for special cases. In this work, we firstly measured the near-infrared emission spectra corresponding to the O2(1 delta g) --> O2(3 epsilon g-) transition of singlet oxygen of cutaneous Propionibacterium acnes (P. acnes) porphyrin under laser excitation. A comparison of the singlet oxygen production of coproporphyrin, which is produced predominantly from P. acnes, with that of other photosensitizers revealed coproporphyrin to be a highly efficient singlet oxygen generator under ultraviolet light A irradiation on the skin. These results suggest that singlet oxygen can be generated on the skin surface from P. acnes porphyrin under ultraviolet irradiation and induce serious damage to the skin.

Coproporphyrins↗
PubMed1996

Nitric oxide release from kidneys of hypertensive rats treated with imidapril.

To examine whether endothelial dysfunction in hypertension is reversible or not, we studied the effects of imidapril, an angiotensin-converting enzyme inhibitor, on nitric oxide release in stroke-prone spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. After a 4-week treatment with imidapril (1 or 10 mg/d SC) or vehicle, acetylcholine-induced vasodilation and nitric oxide release in the isolated kidneys were determined. Nitric oxide release was measured by a chemiluminescense assay. Imidapril lowered blood pressure in stroke-prone SHR in a dose-dependent manner. Untreated stroke-prone SHR exhibited significantly attenuated responses to acetylcholine (10(-8) mol/L) of both renal perfusion pressure (stroke-prone SHE 42 +/- 4% versus Wistar-Kyoto rats [WKY] 58 +/- 4% [mean +/- SE], P < .01) and nitric oxide release (stroke-prone SHR +7.6 +/- 2.1 versus WKY +29.7 +/- 9.7 fmol/min per gram of kidney wt, P < .01). Imidapril at 10 mg/d significantly increased acetylcholine-induced renal vasodilation and nitric oxide release in stroke-prone SHR (renal perfusion pressure, 56 +/- 3%; nitric oxide release, +27.1 +/- 6.4 fmol/min per gram of kidney wt; both P < .01 versus stroke-prone SHR treated with vehicle). On the other hand, imidapril neither decreased blood pressure nor changed nitric oxide release induced by acetylcholine in DOCA-salt hypertensive rats. Staining for endothelial nitric oxide synthase and brain nitric oxide synthase was clearly detected in the kidneys of both stroke-prone SHR and WKY, whereas staining intensity was weaker in DOCA-salt hypertensive rats. Inducible nitric oxide synthase immunoreactivity was barely noticeable in any type of rat. Thus, imidapril restored endothelial damage by pressure-dependent mechanisms. Most of the nitric oxide detected in the perfusate seemed to be derived from constitutive nitric oxide synthase.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Novel detection method of nitric oxide using horseradish peroxidase.

Nitric oxide (NO) readily makes corresponding complexes not only with ferrous iron but also with ferric iron. However, NO-ferric complexes of many heme proteins were unstable, while horseradish peroxidase formed the very stable NO-ferric porphyrin complex with a shift of the Soret band of the absorption wavelength from 396.5 nm to 420.0 nm. The concentration of NO in aqueous media could be monitored by measuring the absorption changes, and the detection limit was 10 nM. The simple procedure is convenient for concentration determination of NO solution.

Calibration↗
PubMed1996

Measurement of 1268 nm emission for comparison of singlet oxygen (1 delta g) production efficiency of various dyes.

Singlet oxygen generation from laser-excited photosensitive dyes was measured directly using a sensitive near-infrared emission spectrometer to monitor the O2(1 delta g)-->O2(3 sigma -g) transition at 1268 nm. The emission intensity was proportional to both the laser power and the concentration of the dyes. The singlet oxygen producing ability of the dyes was compared with that of eosin YS as a standard in methanol. The relative efficiencies of singlet oxygen generation were determined for rose bengal, erythrosine B, phloxine B and eosin YS as 2.39, 1.73, 1.38, 1.00, respectively, while uranine showed no emission in this spectral region. Using rose bengal, erythrosine B, phloxine B and eosin YS, the efficiency of singlet oxygen generation correlated with the photobleaching reaction rate of azo-dyes by these dyes, suggesting singlet oxygen to be a species responsible for causing the photobleaching of azo-dyes. The halogen substituent effect on the efficiency of singlet oxygen generation from laser-excited photosensitive dyes was also examined systematically.

Azo Compounds↗
PubMed1995

Direct measurements of endothelium-derived nitric oxide release by stimulation of endothelin receptors in rat kidney and its alteration in salt-induced hypertension.

BACKGROUND: Stimulation of endothelin subtype B (ETB) receptors has been proposed to induce release of endothelium-derived nitric oxide (EDNO). METHODS AND RESULTS: To obtain direct evidence of its release and its alteration in deoxycorticosterone acetate (DOCA)-salt hypertension, EDNO released from renal vessels by ET stimulation was assayed by a highly sensitive chemiluminescence method. Kidneys were isolated from DOCA-salt and control rats, and renal perfusion pressure (RPP) and EDNO (by hydrogen peroxide-luminol chemiluminescence) in the perfusate were monitored simultaneously during perfusion of ET-1, ET-3, an ETA receptor antagonist (BQ-123), and an ETB receptor agonist (BQ-3020). In control rats, ET-1 and ET-3 dose-dependently increased both RPP and NO release. Although the vasoconstricting effects of ET-1 were greater, their NO-releasing effects were comparable. The increase in NO release by ETs was inhibited by NG-monomethyl-L-arginine. After 10(-6) mol/L BQ-123 treatment, ET-1 decreased RPP and increased NO release in control kidneys. DOCA-salt rats responded to these agents with much less NO release. BQ-3020 at up to 10(-10) mol/L caused vasodilation (RPP, 10(-11) mol/L, -5.4 +/- 1.7%, P < .01) associated with increased NO release in control kidneys (+9.0 +/- 2.7 fmol.min-1.g-1 kidney wt, P < .01). However, in DOCA-salt kidneys, BQ-3020 caused renal vasoconstriction (RPP, +5.4 +/- 2.4%, P < .01 versus control) and a much smaller NO release (+1.1 +/- 0.4 fmol.min-1.g-1 kidney wt, P < .01 versus control). Northern blot analysis revealed that renal ETB mRNA was significantly decreased in DOCA-salt rat kidneys compared with controls (0.36 +/- 0.13 versus 1.00 +/- 0.23, P < .05). CONCLUSIONS: These results suggest that ET-1 and ET-3 release EDNO via ETB receptors in renal vessels. ETB-mediated NO release was reduced in DOCA-salt rats, which may modulate renal function and thus blood pressure regulation in DOCA-salt hypertensive rats.

Animals↗
PubMed1995

Endothelium-derived relaxing factors in the kidney of spontaneously hypertensive rats.

Acetylcholine (ACh)-induced vasodilation is mainly due to endothelium-derived nitric oxide (EDNO) and hyperpolarizing factor (EDHF). To explore the mechanisms underlying attenuated endothelium-dependent vasodilation in hypertensive arteries, we measured the EDNO released from isolated kidneys of spontaneously hypertensive rats (SHR) using a sensitive chemiluminescence assay system of NO. ACh-induced renal vasodilation was significantly smaller in SHR than in the normotensive control, Wistar-Kyoto rats (WKY). However, ACh-induced NO release did not differ between SHR and WKY (10(-7) M: SHR +37 +/- 2 [SE] vs. WKY +32 +/- 4 fmol/min/g kidney). Perfusion with a 20 mEq/L high-K+ buffer, which is reported to inhibit action of EDHF, significantly reduced ACh-induced vasorelaxation in WKY but not in SHR, resulting in identical renal perfusion pressure in SHR and wKY under these conditions. These results indicate that attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF rather than that in EDNO.

Acetylcholine↗
PubMed1995

Application of chemical cytochrome P-450 model systems to studies on drug metabolism--VIII. Novel metabolism of carboxylic acids via oxidative decarboxylation.

The oxidative decarboxylation of carboxylic acids by the chemical cytochrome P-450 model and rat liver microsomal systems was investigated. In the chemical system using meso-tetrakis(pentafluorophenyl)porphyrin iron chloride [Fe(TPFPP)Cl] with iodosylbenzene (PhIO), alpha-arylcarboxylic acids and alpha,alpha,alpha-trisubstituted acetic acids are converted to the corresponding one-carbon-reduced alcohol (I) and carbonyl derivatives (II) via oxidative decarboxylation. These products were then used as standards to identify the metabolites in vivo and in vitro. Biliary excretion of Ia and IIa in bile duct-cannulated rats after oral administration of ketoprofen amounted to 0.22 and 0.03% of the dose, respectively. In the case of indomethacin, Ib and IIb were detected as metabolites in the rat liver microsomal system, in yields of 2.8 and 0.29%, respectively. Further, the yields of Ib and IIb were decreased in the presence of SKF-525A. Thus, these metabolites were formed by cytochrome P-450-dependent reactions. Metabolites Ia, Ib, IIa and IIb had moderate to strong inhibitory activities on arachidonic acid-induced platelet aggregation and cyclooxygenase activity in vitro, comparable to those of the parent compounds.

Animals↗
PubMed1995

1-Benzyl-1,2,3,4-tetrahydroisoquinoline as a parkinsonism-inducing agent: a novel endogenous amine in mouse brain and parkinsonian CSF.

1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) was detected as a novel endogenous amine in mouse brain and parkinsonian CSF by using the gas chromatography-selected ion-monitoring method. The level of 1BnTIQ was very high in CSF of some parkinsonian patients compared with that of controls with other neurological diseases, the mean value being three times higher (parkinsonians: 1.17 +/- 0.35 ng/ml of CSF, n = 18; vs. controls: 0.40 +/- 0.10 ng/ml of CSF, n = 11; mean +/- SEM, not significantly different). The pole test, a toxicological examination to evaluate behavior abnormalities related to Parkinson's disease, was used to examine the pharmacological effect of 1BnTIQ in mice. Repeated administration of 1BnTIQ induced behavior abnormalities, which pretreatment with 1-methyl-1,2,3,4-tetrahydroisoquinoline could prevent. We suggest that 1BnTIQ may be related to the idiopathic Parkinson's disease.

Animals↗
PubMed1994

Analysis of urinary and biliary metabolites of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1-piperidinyl]butyric acid in rats by liquid chromatography-frit-fast atom bombardment mass spectrometry.

The urinary and biliary metabolites of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1-piperidinyl]butyric acid [(+)-MPPB] were examined in rapid-metabolizing (RM) and slow-metabolizing (SM) male Sprague-Dawley rats by means of liquid chromatography-frit-fast atom bombardment mass spectrometry. In the RM-phenotyped rats, unchanged (+)-MPPB could not be detected in urine or bile, but 4-carboxyphenyl-MPPB was detected in bile. In the SM-phenotyped rats, unchanged (+)-MPPB was detected in bile and unchanged (+)-MPPB and beta-oxidized MPPB in urine. Thus, the inter-individual difference in (+)-MPPB metabolism in rats was confirmed in vivo.

Animals↗
PubMed1994

Novel metabolic pathway of arylethers by cytochrome P450: cleavage of the oxygen-aromatic ring bond accompanying ipso-substitution by the oxygen atom of the active species in cytochrome P450 models and cytochrome P450.

We have found a novel metabolic pathway of arylethers, involving the cleavage of the oxygen-aromatic ring bond. When p-(p-nitrophenoxy)phenol was utilized as a substrate, cleaved products, p-nitrophenol and p-benzoquinone, were formed in two cytochrome P450 model systems, meso-tetraphenylporphinatoiron(III) chloride-NaBH4/O2 system and meso-tetrakis (2,6-difluorophenyl)porphinatoiron(III) chloride-m-chloroperoxybenzoic acid (mCPBA) system. Rat liver microsomes also catalyzed this reaction, which was inhibited by a cytochrome P450-specific inhibitor, and it was confirmed that this cleavage proceeded in vivo. Further, experiments using [18O]mCPBA and 18O2 proved that the cleavage reaction is accompanied with the ipso-substitution by the oxygen atom of the active species in both cytochrome P450 model system and cytochrome P450. When the microsomal reactions of p-(p-nitrophenoxy)phenol analogues which lack a hydroxy group, namely p-nitrophenoxybenzene, p-(p-nitrophenoxy)anisole, and p-(p-nitrophenoxy)toluene, were investigated, the cleavage reaction occurred via p-(p-nitrophenoxy)phenol in the cases of p-nitrophenoxybenzene and p-(p-nitrophenoxy)anisole, indicating that a hydroxy group at the p-position to the ether bond is necessary for this pathway. This metabolic pathway appears to be important, because a diarylether linkage, which is very stable and has generally been thought to resist metabolism, is cleaved and benzoquinone, a highly toxic metabolite, is formed.

Animals↗
PubMed1994

Identification of a novel sugar, 4-amino-4,6-dideoxy-2-O-methylmannose in the lipopolysaccharide of Vibrio cholerae O1 serotype Ogawa.

A novel sugar in the lipopolysaccharide of Vibrio cholerae O1 serotype Ogawa has been identified. The sugar was liberated from the lipopolysaccharide when hydrolyzed in 10 M HCl at 90 degrees C for 15 min. The sugar was purified and identified as 4-amino-4,6-dideoxy-2-O-methylmannose (2-O-methylperosamine). Since it was found only in the lipopolysaccharide of Vibrio cholerae O1 serotype Ogawa, it seems that the sugar is one of the specific constituents determining Ogawa serotype specificity.

Carbohydrate Conformation↗
PubMed1994

Long-term administration of L-arginine improves nitric oxide release from kidney in deoxycorticosterone acetate-salt hypertensive rats.

To examine the effects of L-arginine (L-Arg) on endothelial function, we administered 0.5 g/L L-Arg in drinking water to deoxycorticosterone acetate (DOCA)-salt rats for 8 weeks and then measured nitric oxide (NO) release from isolated kidneys using a newly developed real-time chemiluminescence method. Renal pathology was also analyzed. Acetylcholine caused much smaller declines in renal perfusion pressure (10(-7) mol/L acetylcholine: -24 +/- 2% [SEM] versus -50 +/- 2%, P < .001) and NO release in DOCA-salt rats (+3 +/- 1 versus +33 +/- 3 fmol/min per gram kidney weight, P < .001) compared with control rats. L-Arg did not influence the time course of systolic blood pressure elevation in DOCA-salt rats (211 +/- 5 versus 208 +/- 6 mmHg, DOCA versus L-Arg/DOCA, P = NS). However, oral administration of L-Arg improved acetylcholine-induced declines in renal perfusion pressure (10(-7) mol/L acetylcholine: L-Arg/DOCA, -39 +/- 3%, P < .01 versus DOCA). This change was associated with an increase in NO release by acetylcholine (10(-7) mol/L acetylcholine: L-Arg/DOCA, +10 +/- 1 fmol/min per gram kidney weight, P < .05 versus DOCA). However, morphological changes in renal vessels and glomeruli were similar between DOCA and L-Arg/DOCA rats. These results suggest that L-Arg administration partially reverses renal endothelial function with respect to vasorelaxation and NO release independent of blood pressure changes, indicating that hypertensive vessels seem to be depleted of L-Arg and/or have defects in the availability of L-Arg for NO synthesis.

Acetylcholine↗
PubMed1994

Toxicity of singlet oxygen generated thermolytically in Escherichia coli.

Three water-soluble derivatives of naphthalene endoperoxide were prepared to examine the toxicity of singlet oxygen towards Escherichia coli. On incubation without irradiation, these endoperoxides produce singlet oxygen thermolytically in a dose-dependent manner. The amount of singlet oxygen produced per unit time can be controlled by varying both the incubation temperature and the number of methyl substituents of the naphthalene endoperoxide derivatives. 3-(1,4-Dihydro-1,4-epidioxy-4-methyl-1-naphthyl)propionic acid (EP-1), one of the derivatives, inhibited E. coli growth dose- and incubation temperature-dependently and caused E. coli lethality. Furthermore, EP-1 did not induce superoxide dismutase or catalase in E. coli even when the cells were incubated in nutritionally rich medium containing trypticase/soy/yeast extract. Singlet oxygen, one of the reactive oxygen species, did not act as a signal for induction of superoxide dismutase and catalase, in contrast to the actions of superoxide and hydrogen peroxide.

Escherichia coli↗
PubMed1993

Real time measurement of nitric oxide produced ex vivo by luminol-H2O2 chemiluminescence method.

Endothelium-derived relaxing factor, identified as nitric oxide (NO), is derived from a guanidino nitrogen of L-arginine via its metabolism by nitric oxide synthase. A newly developed aqua-chemiluminescence system was used to measure the amount of NO release from the isolated, perfused rat kidney concomitantly with the pressure changes (Kikuchi, K., Nagano, T., Hayakawa, H., Hirata, Y., and Hirobe, M. (1993) Anal. Chem. 65, 1794-1799). In normotensive rats, basal NO release was estimated to be 86 +/- 6 fmol min-1 (g of kidney weight)-1, and endothelium-dependent vasodilators increased NO release with a concomitant pressure reduction. Pretreatment of the kidney with detergents to damage the vascular endothelium diminished the responses of NO and perfusion pressure to acetylcholine, while infusion of authentic NO solution caused an increase in the chemiluminescence and a concomitant decrease in the pressure. The half-life of NO in O2-saturated Krebs-Henseleit buffer was determined as 6.41 s, and the decay constant (Kd) was 0.108 s-1. The measuring system involves a lag time of 15 s after passage of the solution through the kidney, so that the measured value is 13.0% of the true luminal NO concentration in the kidney, up to 400 pM. These observations enabled us to quantitate the degree to which NO released from the rat kidney changes perfusion pressure. Acetylcholine-induced vasodilation and NO release were markedly attenuated in deoxycorticosterone acetate-salt hypertensive rats, in which the endothelium is known to be markedly damaged. Thus, this assay system may make it possible to evaluate the extent of injury to the endothelium in conditions involving vascular damage.

Acetylcholine↗
PubMed1993

Methamphetamine antagonistic property of (+)- and (-)-4-phenyltetrahydroisoquinoline in rat anococcygeus muscle.

The antagonistic effects of (+)- and (-)-4-phenyl-1,2,3,4-tetrahydroisoquinoline (4PTIQ) on methamphetamine in the rat anococcygeus muscle were compared with those of cocaine and nomifensine. Methamphetamine contracted the anococcygeus muscle through the release of norepinephrine from noradrenergic nerve terminals. (+)-4PTIQ inhibited the methamphetamine-induced contractions more strongly than cocaine and nomifensine. (+)-4PTIQ had no potentiating effects on exogenous norepinephrine-induced contraction, which was considered to be an index of amine neuronal uptake blockade. On the other hand, (-)-4PTIQ, cocaine and nomifensine produced a significant leftward shift of the norepinephrine concentration-response curve, i.e. they showed a strong blocking effect on amine neuronal uptake. These results suggest that the inhibitory effects of (+)-4PTIQ on the action of methamphetamine are mediated by a mechanism other than inhibition of amine neuronal uptake.

Animals↗