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Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 451 records · Page 25Linked to original sources

Predominance of beta-structure in solubilized zona pellucida from porcine ova.

The isolated zona pellucida from porcine ova was effectively solubilized in water at 60 degrees C within one hour. The circular dichroic spectra of zona in water with and without dithiothreitol showed the beta-form. Although sodium dodecyl sulfate partially induced helical structure, the beta-form was considerably retained. These results indicate that the zona glycoproteins have a structure-forming potential for the beta-structure and the hydrogen bonds of the beta-structure stabilize the supramolecular complex of the zona pellucida. The beta-form was also detected in zona solubilized by tryptic digestion. Porcine acrosin, however, did not solubilize the zona.

Animals↗

The role of the N-terminus in the active conformation of the substance P analogues.

The role of the N-terminus in the activity of substance P analogues was studied with the isolated rat spinal cord and the guinea-pig ileum. When the C-terminal Leu10 or Met11 was replaced by the D-isomer, the analogues without the N-terminal tetrapeptide were 40-100 times less potent than those with the N-terminus in both motoneuron-depolarizing and ileum-contracting actions. These results that the N-terminus may stabilize the active conformation of the substance P analogues.

Amino Acids↗

Two steps in ATP-dependent shape change of human erythrocyte ghosts.

Most human erythrocyte membranes (ghosts) prepared with 10 mM Tris-Cl buffer were spherocytic and changed shape through crenated to discoidal in the presence of 2 mM Mg-ATP at 37 degrees C during 30 min under hypotonic conditions. These discocytic ghosts reverted to spherical form after being washed with 1 mM MgCl2, although their membranes were phosphorylated and they were converted to discocytes again, immediately on addition of 2 mM Mg-ATP, even at 6 degrees C. There seem to be 2 steps in the shape change of the ghosts; the first step proceeds gradually during incubation at 37 degrees C for 30 min in the presence of a physiological concentration of Mg-ATP and the second step occurs rapidly after addition of Mg-ATP even at 6 degrees C. This suggests that not only membrane phosphorylation but also specific ATP-binding (or hydrolysis) is necessary for erythrocyte shape change.

Adenosine Triphosphate↗

Synthetic analogues and biosynthetic intermediates of bleomycin. Metal-binding, dioxygen interaction, and implication for the role of functional groups in bleomycin action mechanism.

In order to clarify the role of bleomycin functional groups in action mechanism, the metal-binding, dioxygen activation, and DNA cleavage of several synthetic analogues and biosynthetic intermediates of bleomycin have been investigated. The present results support that 1) the beta-aminoalaninepyrimidine-beta-hydroxyhistidine portion of the bleomycin molecule substantially participates in the Fe(II) and dioxygen interactions, 2) the transposition of the pyrimidine (or pyridine) and imidazole groups in the Fe(II)-coordination is essential for the effective binding and activation of molecular oxygen by the bleomycin ligands, and 3) the gulose-mannose moiety plays an important role as an environmental factor for the efficient dioxygen reduction and DNA cleavage, although the sugar portion does not contribute significantly to the nucleotide specificity in the DNA strand scission. Certain oligopeptides are able to mimic the metal-binding and dioxygen activation by bleomycin, but not induce the effective DNA cleavage. Probably, the bithiazole DNA interaction site of bleomycin delivers the iron/dioxygen chemistry to particularly the DNA (formula, see text) nucleotide sequences.

Base Sequence↗

Purification and some properties of neuraminidase isolated from the culture medium of oral bacterium Streptococcus mitis ATCC 9811.

Neuraminidase acting on the salivary bacterial agglutinating factor was isolated and purified from the culture medium of Streptococcus mitis ATCC 9811. The molecular weight and the isoelectric point of the enzyme were determined to be 42,000 and a pH of 4.6, respectively. The enzyme showed high activity against human glycoprotein substrates, especially the salivary bacterial agglutinating factor.

Electrophoresis, Polyacrylamide Gel↗

Metabolism of afloqualone, a new centrally acting muscle relaxant, in monkeys and dogs.

The disposition and metabolism of afloqualone [6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone, AFQ] were studied in monkeys and dogs after oral administration of 14C-AFQ. In both species the blood radioactivity reached a maximum 1 to 2 h after the administration, and decreased with apparent half-lives of 3.2 h in the monkey and 7.2 h in the dog. A total of about 90% of the administered radioactivity was recovered from the urine (monkey, 72.3%; dog, 51.8%) and feces (monkey, 19.4%; dog, 36.7%) within 4 or 5 d. AFQ was extensively metabolized in both species. There were species differences in the composition of the urinary metabolites. In the dog, AFQ was monohydroxylated at the 2-, 2'-, 3'- and principally 4'-position and each metabolite was further conjugated with glucuronic acid. N-Acetylated metabolites were not detected. In the monkey, N-acetylation was the main initial step of metabolism followed by hydroxylation at the acetyl-methyl, 2'-methyl and 2-fluoromethyl groups. Phenolic metabolites such as 3'- and 4'-hydroxylated AFQ were not detected. Both animals excreted sulfur-containing metabolites such as the 2-methylthio, 2-methylsulfinyl and 2-methylsulfonyl derivatives of AFQ.

Animals↗

Role of substance P as a sensory transmitter in spinal cord and sympathetic ganglia.

The hypothesis that substance P (SP) might be a transmitter of primary sensory neurons was first proposed by Lembeck in 1953. A large amount of evidence supporting this hypothesis has recently accumulated, particularly since the elucidation of the chemical structure of SP by Leeman and her colleagues in 1971, which made a number of new approaches possible (e.g. radioimmunoassay for SP, immunohistochemistry and electrophysiological tests of SP action on central and peripheral neurons). SP is concentrated in certain primary afferent terminals in the spinal cord, is released therefrom when the dorsal roots are electrically stimulated, and exerts a powerful excitant action on spinal neurons. It is therefore likely that SP produces excitatory postsynaptic potentials (EPSPs) in spinal neurons, although the characteristics of SP-mediated EPSPs, i.e. their time course, ionic mechanisms, etc., remain to be revealed. Recent electrophysiological and neurochemical studies on the prevertebral ganglia of the guinea-pig strongly suggest that SP is released from axon collaterals of visceral primary afferent neurons in the ganglia and serves as a transmitter that generates non-cholinergic slow EPSPs in principal cells. There is evidence that this SP-mediated synaptic transmission in the sympathetic ganglia is under the influence of enkephalinergic presynaptic inhibition. Some preliminary experiments on the interaction between SP and enkephalins in the spinal cord are described.

Action Potentials↗

Substance P as an excitatory transmitter of primary afferent neurons in guinea-pig sympathetic ganglia.

Electrophysiological and neurochemical experiments were carried out to examine a possible transmitter role substance P in the prevertebral ganglia of the guinea-pig. When potentials were recorded intracellularly from neurons of the isolated ganglia, stimulation of the pre- or postganglionic nerves elicited a non-cholinergic slow excitatory postsynaptic potential (EPSP). This synaptic potential was compared with the effects of substance P. Brief application of substance P caused a depolarization of the ganglion cells with a similar time course to that of the non-cholinergic slow EPSP. Changes in membrane resistance during the substance P-induced depolarization resembled those associated with the non-cholinergic slow EPSP. During the substance P-induced depolarization the non-cholinergic slow EPSP was markedly depressed. Attempts were made to determine the origin of the fibers eliciting the non-cholinergic slow EPSP. In the inferior mesenteric ganglia isolated together with preganglionic nerves that retained intact connections with spinal nerve roots, dorsal root stimulation evoked a non-cholinergic slow EPSP but not a cholinergic fast EPSP in the ganglion cells, whereas ventral root stimulation caused only cholinergic fast EPSPs. Following the prolonged treatment with capsaicin, the non-cholinergic slow EPSP was greatly depressed or abolished. Radioimmunoassay revealed that after ligation or section of pre- or postganglionic nerves an accumulation of substance P occurred in the proximal stumps of the interrupted nerves. Stimulation with high potassium medium evoked a release of immunoreactive substance P from the prevertebral ganglia and the release was calcium-dependent. The present findings suggests that axon collaterals of certain visceral primary efferents form synapses with principal cells in the prevertebral ganglia and release substance P as a transmitter for the non-cholinergic slow EPSP.

Adrenergic Fibers↗

Effect of timepidium bromide, an anticholinergic agent, on gastric and duodenal blood flow distribution in rabbits.

Effects of timepidium bromide (TB; anticholinergic agent), acetylcholine (ACh) and neostigmine (Neost) on gastric and duodenal blood flow distribution were studied by the use of 131I-labeled macroaggregated human serum albumin (MAA) in rabbits. In normal rabbits, gastric blood flow was found to be uneven in various regions of the stomach: anterior corpus (50% of total gastric blood flow) greater than posterior corpus (40%) greater than pyloric antrum (7%). Intravenous administration of TB (200 microgram/kg) to normal rabbits produced a slight increase in total gastric blood flow, but the increase in the mucosal layer of the pyloric antrum was considerable. On the other hand, ACh (10 microgram/kg, i.v.) and Neost (50 microgram/kg. i.v.) significantly reduced the total gastric blood flow, in particular, the mucosal blood flow in the anterior and posterior corpus. This reduction in blood flow was virtually abolished by TB and was restored to the normal level. These results suggest that these cholinergic or anticholinergic drugs affect the gastric blood flow and that these effects may be mediated through muscarinic receptors. Blood flow in the duodenum was only slightly changed by these drugs.

Acetylcholine↗