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Biomedical subjects

S Satoh

Publications and source records attributed to S Satoh.

At least 811 records · Page 45Linked to original sources
PubMed1984

Biosynthesis of astromicin and related antibiotics. I. Biosynthetic studies by bioconversion experiments.

Biosynthesis of astromicin, a unique pseudodisaccharide aminoglycoside antibiotic containing 1,4-diaminocyclitol component, was investigated by isolating a variety of possible precursor compounds from mutants of Micromonospora olivasterospora in which biosynthetic pathways for astromicin were blocked. Washed mycelia of M. olivasterospora mutants converted these compounds to astromicin, which was detected by thin-layer chromatography. Since astromicin possesses one glycyl and three methyl groups, [14C]glycine and [14C]methionine should be incorporated into precursors to form astromicin. To confirm the biosynthetic pathway, formation of labeled astromicin from the precursors was examined using [1-14C]-glycine or [methyl-14C]methionine. From above results, we propose the biosynthetic pathway for astromicin as shown in Fig. 2.

Aminoglycosides↗
PubMed1984

Biosynthesis of astromicin and related antibiotics. II. Biosynthetic studies with blocked mutants of Micromonospora olivasterospora.

An inosamine-idiotrophic mutant, KY11559, which produced no astromicin unless scyllo-inosamine was added to the fermentation medium, was isolated from Micromonospora olivasterospora. Biotransformation studies were performed with resting cells of this mutant and compounds assumed to be precursors of 1,4-diaminocyclitol (fortamine). Scyllo-inosose, scyllo-inosamine and FU-10 were converted to astromicin. A number of mutants blocked in the biosynthesis of astromicin were developed from M. olivasterospora, and the intermediates accumulated by these mutants were isolated and identified. Twenty-five blocked mutants were classified into 10 groups, based on their complementation patterns by cosynthesis experiments. Further, utilizing these blocked mutants and the isolated compounds, biotransformation analyses were performed. The results showed that the amination at position 4 in fortamine occurred after formation of the pseudodisaccharide. Subsequently, the aminosugar and aminocyclitol moieties were aminated, methylated, dehydroxylated, epimerized and acylated to produce astromicin. Thus it was demonstrated that the astromicin biosynthetic pathway has a unique feature which is not found in the biosynthesis of other aminoglycoside antibiotics.

Aminoglycosides↗
PubMed1984

Shift of metabolism in rats with ventromedial hypothalamic lesions with respect to changes in daily rhythms of enzyme activity.

Metabolic alterations in ventromedial hypothalamus (VMH)-lesioned rats were investigated by examining daily changes of enzyme activities and urea concentrations three weeks after the operation. VMH-lesions in female adult rats caused a significant elevation in the activity of acetyl-CoA carboxylase in the liver and parametrial adipose tissue. These changes suggest an increased lipogenesis. VMH-lesions also elicited an increase in activities of glucokinase (GK), pyruvate kinase (PK) and fructose 1,6-bisphosphatase (FBPase), and a decrease in activities of phosphofructokinase (PFK), glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver. The apparently inconsistent changes in activities of key glycolytic enzymes, GK, PK and PFK, and key gluconeogenic enzymes, G6Pase, PEPCK and FBPase in the liver may be explained by the fact that they were favorable for glucose oxidation through pentose phosphate cycle and provide NADPH for lipogenesis in the liver. Furthermore, VMH-lesions induced an increase in urea contents of the liver and serum, and elicited an increase in activity of liver tyrosine aminotransferase (TAT) and a decrease in activity of liver histidase. These changes suggest an accelerated amino acid and protein catabolism, and favor an increment in the supply of the substrate for lipogenesis. Daily rhythms of TAT, histidase activities and serum urea concentration observed in the control rats were abolished by VMH-lesions. These findings suggest that VMH-lesions elicit the loss of these daily rhythms, probably through the disturbance of the circadian rhythm of feeding behavior at this dynamic phase (three weeks after operation) of obesity.

Acetyl-CoA Carboxylase↗
PubMed1984

Effects of K-351 on hemodynamics and renin release in anesthetized dogs.

Effects of K-351 (3,4-dihydro-8-(2-hydroxy-3-isopropyl-aminopropoxy)-3-nitroxy++ +-2H-1-benzopyran) on hemodynamics and renin release were investigated in pentobarbital anesthetized dogs. K-351 (0.3 mg/kg, i.v.) significantly decreased systemic blood pressure, heart rate, mesenteric blood flow, and renin secretion rate without change in renal blood flow. Degree of hypotension and basal plasma renin activity showed significant correlation. In indomethacin-treated (5 mg/kg, i.v.) dogs, K-351 decreased renal blood flow and caused smaller decrease in systemic blood pressure and larger suppression of renin secretion rate than in non-treated dogs. These results suggest that the hypotensive effect of K-351 may be due in part to suppression of the renin-angiotensin system and may be modulated by the prostaglandin system.

Adrenergic alpha-Antagonists↗
PubMed1984

Evidence for prostaglandin-independent mechanisms in renin release mediated by alpha adrenoceptors during renal nerve stimulation in anesthetized dogs.

We investigated alpha adrenoceptor-mediated renin release in relation to renal prostaglandin production in anesthetized dogs. The effects of intrarenally infused phentolamine (5 micrograms/kg/min) on renin and prostaglandin E2 release induced by renal nerve stimulation (RNS, 2.5-5 Hz) were studied in indomethacin (5 mg/kg i.v.)-treated and untreated dogs. In the control group, RNS reduced renal blood flow and increased both renin and prostaglandin E2 secretion rates. Phentolamine inhibited the blood flow response and attenuated the renin response; it did not affect the prostaglandin E2 response. In the indomethacin-treated group, the renal venous plasma prostaglandin E2 concentration was not changed, the renin secretion rate was increased during RNS. Phentolamine also attenuated the renin response in this prostaglandin-depleted state. These results suggest that alpha adrenoceptors participate in renin release induced by RNS and that some of the alpha adrenoceptor-mediated renin release is independent of renal prostaglandins. Prostaglandin release induced by RNS may be mediated by mechanisms other than alpha adrenoceptors.

Anesthesia↗
PubMed1984

[Effects of an anorexiant, mazindol, on metabolic abnormalities of rats with ventromedial hypothalamic lesions].

The present study investigated the effects of mazindol on the metabolic abnormalities of ventromedial hypothalamic-lesioned (VMH) rats. About 200 g female Sprague-Dawley rats were divided into VMH and sham-operated rats. Two weeks later the feeding of a mazindol-containing diet (50 mg/kg) was started in half of each group. Eight weeks after mazindol treatment, rats were sacrificed, and various parameters were determined. Food intake was measured between the 4th and 5th week. In VMH-lesioned rats, mazindol decreased food intake remarkably and restored body weight, Lee Index, organ weights (liver, parametrial fat pad and lung), serum insulin, serum lipids (cholesterol, triglyceride, phospholipid and free fatty acids), serum GOT GPT, total lipid in the liver and findings of liver history to normal. Mazindol did not change these parameters, except for serum triglyceride, in sham-operated rats and had no effect on food intake. The results suggested that normalization of these abnormalities in VMH-lesioned rats depends mainly on the reduction of food intake due to overresponse to mazindol by VMH lesions.

Animals↗
PubMed1984

Distribution of filipin-sterol complexes in rat hepatocytes.

Distribution of cholesterol in rat hepatocytes under normal untreated and phenobarbital-treated conditions was studied by freeze-fracturing using filipin. In untreated rat hepatocytes, filipin-sterol complexes were observed on intercellular plasma membranes as well as on lysosomes and microbodies. These complexes were evenly distributed. In phenobarbital-treated rat hepatocytes, filipin-sterol complexes in the lysosomes or microbodies were distributed unevenly. In the bile canaliculi, no filipin-sterol complexes were noted. Based on these findings, the functional state of the organellae concerned was discussed.

Alkaline Phosphatase↗
PubMed1984

Effect of verapamil on renal vasoconstriction induced by angiotensin II, norepinephrine or renal nerve stimulation in anesthetized dogs.

The effect of verapamil on the decrease in renal blood flow (RBF) induced by angiotensin II (Ang II), norepinephrine (NE) or renal nerve stimulation (RNS) was examined in pentobarbital-anesthetized dogs. The injection into the renal artery of Ang II (0.01-0.1 micrograms), or NE (0.1-1.0 micrograms), or RNS (1-10 Hz) decreased RBF in a dose- or frequency-dependent manner. The renal arterial infusion of verapamil (30 micrograms/min followed by 100 micrograms/min) brought about a sustained increase in RBF and inhibition of renal vasoconstriction induced by Ang II or NE, but not by RNS, when the extent of vasoconstriction was estimated in terms of absolute changes in RBF. We also observed that the inhibitory effect of verapamil on Ang II-induced vasoconstriction was greater than on NE-induced constriction, as estimated from the % change in RBF. These results indicate that in canine renal vasculature, verapamil exerts different inhibitory effects on the vasoconstriction induced by Ang II, NE or RNS.

Anesthesia↗
PubMed1983

Effect of protein synthesis inhibitors on the trophic action of the nerve stump.

We report that protein synthesis inhibitors exert an inhibitory effect on the trophic action of the nerve stump. The sciatic nerve innervating the extensor digitorum longus muscles of mice was cut either as close to, or as far from, the muscle as possible. Denervation changes in the muscle were evaluated using the resting membrane potential and dose-response curves obtained by plotting acetylcholine-induced contractures. Actinomycin D (2 micrograms/kg, i.p.), ethidium bromide (10 micrograms/kg, i.p.), cycloheximide (1 or 5 mg/kg, i.p.), or chloramphenicol (100 mg/kg, p.o.) administration was immediately after neurotomy and continued daily until the day preceding muscle removal. Although denervation changes occurred significantly later in muscles with a long rather than a short nerve stump, the administrated antibiotics, excluding cycloheximide, accelerated the manifestation of denervation changes in muscles with long nerve stumps without affecting those in muscles with short nerve stumps.

Acetylcholine↗
PubMed1983

Involvement of alpha- and beta 1-adrenergic mechanisms in the immobility-reducing action of desipramine in the forced swimming test.

The influences of various monoaminergic agents on the immobility-reducing action of desipramine (DMI) in the forced swimming test were examined. 5-Methoxy-N,N-dimethyltryptamine and methysergide, a serotonin agonist and antagonist, respectively, did not affect the duration of immobility. Pimozide, a dopamine antagonist, prolonged the duration of immobility at a dose of 0.5 mg/kg. However, at the doses tested, these drugs had no effect on the action of desipramine. Phenoxybenzamine, an alpha-adrenergic antagonist, prolonged the duration of immobility only with the largest dose (20 mg/kg), but the action of desipramine was completely blocked by this drugs at all doses. Intracerebroventricular injection of a beta-adrenergic agonist, isoproterenol (ISO), and two selective beta 1-adrenergic antagonists, atenolol (ATE) and practolol, dose-dependently diminished and potentiated, respectively, the action of desipramine although these drugs had no effect on the duration of immobility when given alone. A beta 2-adrenergic antagonist derived from oximino-9-fluorene, (IPS 339) did not influence the duration of immobility or affect the action of desipramine. The effect of isoproterenol was almost completely blocked by the pretreatment with atenolol and practolol but not by IPS 339. Subcutaneously-injected isoproterenol did not affect the action of desipramine. Isoproterenol and atenolol had no effect on the concentration of desipramine in brain regions. Phenylephrine, a postsynaptic alpha-adrenergic agonist, reduced the duration of immobility as did desipramine, but this action was not affected by isoproterenol and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Inhibition of cardiac sympathetic neurotransmission by histamine in the dog is mediated by H1-receptors.

1 The role of histamine H1- and H2-receptors in mediating prejunctional inhibition of cardiac sympathetic neurotransmission and histamine-induced coronary vasodilatation were investigated in perfused dog hearts in situ. 2 Intra-arterial injections of histamine into the right coronary artery during the resting state caused slightly positive chronotropic responses in doses larger than 1 microgram. 3 Histamine in doses of 0.1 to 10 micrograms into the right coronary artery reduced the tachycardia resulting from electrical stimulation of the cardiac sympathetic nerves. 4 Intra-coronary infusions of chlorpheniramine (300 micrograms/min) significantly reduced the histamine-induced depression of cardiac nerve stimulation. The effects of cimetidine (300 micrograms/min) and metiamide (300 micrograms/min) were less pronounced. 5 Histamine (1 to 10 micrograms) further increased heart rate resulting from the continuous intra-coronary infusion of noradrenaline (1 or 3 micrograms/min). 6 Intra-arterial injections of histamine (0.1 to 10 micrograms) caused an increase in coronary blood flow in a dose-dependent manner. This was partially inhibited by intra-coronary infusion of chlorpheniramine (10 to 300 micrograms/min) and by cimetidine (10 to 300 micrograms/min). The combination of both drugs (10 to 100 micrograms/min of each) caused a larger inhibition. 7 The present results suggest that the histamine-induced depression of heart rate during cardiac sympathetic nerve stimulation is due to a prejunctional effect mediated mainly by H1-receptors. Histamine-induced coronary vasodilatation in the dog is mediated both by H1- and H2-receptors.

Animals↗
PubMed1983

Urethral response to nerve stimulation measured by strain gauge force transducer.

This paper presents a study of urethral responses to efferent nerve stimulation in dogs. The pelvic, hypogastric and pudendal nerves were stimulated using a programmed instrument under three different in vivo conditions. The preparations consisted of: (A) bladder, urethra, and rectum; (B) urethra and rectum, and (C) urethra only. Stimulation of the pelvic nerve in preparation A resulted in elongation and constriction of the mid and proximal urethra with a resultant rise in pressure. However, this response was reduced in preparations B and C. Similar observations were made with hypogastric nerve stimulation. The results of pudendal nerve stimulation were significantly different, in that the pressure rise occurred in the mild and distal urethra and varied in elongation response.

Animals↗
PubMed1983

Different mode of action between norepinephrine and phenylephrine on prostaglandin synthesis by dog renal inner medullary slices.

The dog renal inner medullary slices synthesized and released prostaglandin (PG) E2, PGF2 alpha, PGI2 (measured as 6-keto-PGF1 alpha) and thromboxane (TX) A2 (measured as TXB2). When incubated in the presence of norepinephrine, the synthesis of these arachidonic acid metabolites were stimulated about 2-fold. The norepinephrine effect could be antagonized by the addition of an alpha-adrenoceptor blocking agent, phenoxybenzamine, but not by a beta-adrenoceptor blocking drug, propranolol. Phenoxybenzamine at concentrations that block norepinephrine stimulation of prostaglandin biosynthesis did not suppress the increase in prostaglandins synthesized by exogenous arachidonic acid. By contrast, phenylephrine caused only PGI2 production without producing other prostaglandins and thromboxane. This phenylephrine effect could not be antagonized by either alpha- or beta-adrenoceptor blocking agents, but it was abolished by the specific PGI2 synthetase inhibitors 15-hydroperoxy arachidonic acid and tranylcypromine. These results suggest that norepinephrine-induced prostaglandin synthesis is mediated via an alpha-adrenergic receptor mechanism, whereas phenylephrine stimulation is primarily occurring at the step which follows the cyclooxygenase reaction in the metabolism of arachidonic acid.

Animals↗
PubMed1983

Further studies on the suppressing effect of isoproterenol on the immobility-reducing action of desipramine in the forced swimming test.

The present study was undertaken to examine whether the suppressing effect of intracerebroventricular (i.c.v.) administration of isoproterenol (ISO) on the immobility-reducing action of desipramine (DMI) in the forced swimming test was mediated through the presynaptic noradrenaline (NA) neurons and presynaptic alpha 2-adrenoceptors in rat brain. As in the case of DMI, phenylephrine (i.c.v.) and yohimbine (i.p.) reduced the duration of immobility. The actions of DMI and yohimbine but not that of phenylephrine were diminished and potentiated by i.c.v. administration of ISO and atenolol, respectively. The suppressing effects of ISO were almost completely blocked by the pretreatment with atenolol. On the other hand, clonidine (s.c.) diminished the action of DMI as did ISO, although clonidine had no effect on the duration of immobility when given alone. The suppressing effect of clonidine was antagonized by the pretreatment with yohimbine at a dose which did not affect the duration of immobility, when given alone, nor influenced the action of DMI, whereas the effect of ISO was not affected by the same dose of yohimbine. These results suggest that the suppressing effect of ISO on the immobility-reducing action of DMI in the forced swimming test is mediated through the presynaptic NA neurons, and ISO acts through the presynaptic beta 1- but not alpha 2-adrenoceptors.

Animals↗