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Biomedical subjects

H Fukuda

Publications and source records attributed to H Fukuda.

At least 1,009 records · Page 56Linked to original sources

Possible mechanism of action of diazepam as an adenosine potentiator.

Diazepam (10(-5)-3 X 10(-4) M) selectively enhanced the negative inotropic responses of guinea-pig atria and the relaxation of guinea-pig taenia coli caused by adenosine and ATP. In the atria, the effect of 2-chloroadenosine, a stable analog of adenosine, was not affected by diazepam. Segments of guinea-pig atria or taenia coli took up 3H-activity during incubation with [3H]adenosine but did not take up 32P-activity from [32P]ATP. Diazepam at concentrations sufficient to enhance the in vitro responses reduced by half the uptake of 3H-activity into the preparations. Adenosine (10(-6) M) and ATP (10(-6) M) were degraded to inactive inosine during incubation with atrial segments and their degradation was inhibited by diazepam. In contrast, in rat atria, diazepam did not enhance the negative inotropic effects of adenosine and ATP, and did not prevent the uptake of adenosine. These results suggest that in guinea-pig atria and taenia coli, diazepam like dipyridamole, acts as an adenosine potentiator by preventing the uptake and degradation of adenosine.

2-Chloroadenosine↗

Diurnal variations of lipogenic enzymes, their substrate and effector levels, and lipogenesis from tritiated water in rat liver.

The activities of glucose-6-phosphate dehydrogenase, malic enzyme, fatty acid synthetase and acetyl-CoA carboxylase (extracted with or without phosphatase inhibitor) in rat liver did not vary significantly during 24 h. The hepatic levels of glucose 6-phosphate and malate increased coordinately 3-6 h after the beginning (1900 h) of food intake and were high until morning, whereas the levels of acetyl-CoA and citrate peaked at 1900 h and then decreased. However, it is remarkable that the in vivo incorporation of 3H from tritiated water into fatty acids in liver increased with the level of malonyl-CoA after food intake. Comparing the substrate and effector levels with the Km and Ka values for the enzymes, the levels of acetyl-CoA, malonyl-CoA and citrate appear to limit the enzyme activities. It is suggested that, after food intake, the physiological activity of acetyl-CoA carboxylase was increased with the substrate increase and/or with the catalytic activation with citrate, and consequently, the fatty acid synthetase activity was also increased, whereas the enzyme activities measured under optimum conditions were not.

Acetyl-CoA Carboxylase↗

Experimental studies on myocardial glucose metabolism of rats with 18F-2-fluoro-2-deoxy-D-glucose.

The myocardial uptake of 18F-FDG was investigated under various conditions, and compared with brain and tumor uptake as a function of blood glucose level. The uptake by the heart of normal feeding rats was rapid and remained essentially unchanged up to 2 h after 18F-FDG injection, approximately 3%-4% dose/g tissue. On the other hand, the myocardial uptake of fasted rats was significantly lower than that of control rats throughout the course of the study, and it was about 0.3%-0.4% dose/g tissue. Myocardial uptake of 18F-FDG was relatively constant at glucose levels under about 120 mg/100 ml and increased steeply at higher blood glucose levels. In contrast, brain uptake decreased linearly with increasing levels of blood glucose, revealing a strong negative correlation between brain uptake of 18F-FDG and blood glucose levels. The tumor uptake pattern remained relatively unchanged, irrespective of blood glucose levels. It was revealed that the glucose demands of brain, heart, and tumor were entirely different. After a glucose load, the myocardial uptake of fasted rats increased only slightly from 0.4% to 0.6% dose/g tissue, in spite of transitional hyperglycemia. In contrast, insulin caused myocardial uptake to increase extraordinarily, although it caused a decrease in blood glucose levels.

Animals↗

The non-GABAergic nature of 3H-baclofen binding in rat peripheral tissues.

In peripheral tissues from organs such as the kidney, liver and spleen, specific binding of 3H-baclofen was most highly detected in the kidney, and that in the liver and spleen was approximately one-tenth that in the kidney. The amount of specific binding did not differ at a room temperature of 20-25 degrees C or 0-4 degrees C, and equilibration occurred within 10 min. Divalent cations (Ca2+, Mg2+, Mn2+ and Ni2+) and monovalent cations (Na+ and K+) did not increase the specific binding, yet in higher concentrations, they decreased both specific and non-specific binding. Specific binding showed a single component, Kd and Bmax of which were 6.35 microM and 79 pmol/mg protein, respectively. The binding was stereospecific; (-)baclofen was 150 times as potent as (+)baclofen. Some of the structural analogues of baclofen inhibited 3H-baclofen binding whereas GABA and its related compounds showed little or no inhibition. Bmax of the binding in the kidney of spontaneously hypertensive rats (SHR) was higher by 28% than that of normotensive Wistar-Kyoto rats (WKY), whereas the Kd values did not differ. These results indicate that specific 3H-baclofen binding in the rat peripheral tissues is entirely different from the binding in the central nervous system (GABAB sites).

Animals↗

Opioid receptor types on adrenergic nerve terminals of rabbit ear artery.

Methionine enkephalin, leucine enkephalin, [D-Ala2, D-Leu5] enkephalin, alpha-neoendorphin, beta-endorphin, dynorphin (1-13) and ethylketocyclazocine inhibited the contractions of rabbit ear artery ring segments elicited by transmural nerve stimulation at 8 Hz. Ethylketocyclazocine, dynorphin (1-13) and leucine enkephalin produced partial inhibition, their apparent intrinsic activities (alpha) being 0.57, 0.75 and 0.66, respectively. Morphine and normorphine, which are agonists at mu-receptors, did not inhibit the response of the artery. Naloxone antagonized the actions of opioids and ethylketocyclazocine, and was more effective against methionine enkephalin, leucine enkephalin and [D-Ala2, D-Leu5] enkephalin than against alpha-neoendorphin, ethylketocyclazocine and dynorphin (1-13). The pA2 values of naloxone against so-called delta-agonists were approx. 8.5, and against so-called kappa-agonists were approx. 7.7. The supposed kappa-antagonist, Mr2266, was more effective than naloxone in antagonizing the actions of alpha-neoendorphin, and the kappa-agonists dynorphin (1-13) and ethylketocyclazocine. The pA2 values of Mr2266 against kappa-agonists were 8.5-9.0, and against delta-agonists were 7.8 or less. The opioid peptides and opioids tested did not cause dilatation of the artery previously contracted with histamine. These results suggest that the opioid peptides and ethylketocyclazocine acted on opioid receptors at adrenergic nerve terminals in the ear artery. The opioid receptors appear to be of the delta- and kappa-types, not the mu-type.

Animals↗

Three serial neurones in the innervation of the colon by the sacral parasympathetic nerve of the dog.

Electrophysiological and histological techniques were used to study the nature of the innervation of the colon by the sacral parasympathetic nerve of the dog. Many cells which incorporate horseradish peroxidase (HRP) were observed in ganglia of the pelvic plexus, but not in the sacral cord, after HRP was injected into the wall of the distal colon. Stimulation of the pelvic ganglia by an application of dimethylphenylpiperazinium contracted the distal colon. The contraction was reduced by nicotine applied to the colon. Compound action potentials in responses of rectal strands of the pelvic nerve to stimulation of the sacral ventral roots decreased or disappeared after hexamethonium bromide (C6) was applied to the pelvic plexus. Conduction velocities of the potentials showed that most of the preganglionic fibres were B fibres, and nearly all the post-ganglionic fibres were C fibres. Many C fibres were observed by electron microscopy in the rectal strands after degeneration of the pelvic and hypogastric nerves. Stimulation of such rectal strands caused a contraction of the colon, which diminished after C6 was applied to the distal colon. These results show that the sacral parasympathetic nerve innervating the colon comprises three serial neurones located in the sacral spinal cord, the pelvic plexus and the myenteric plexus.

Action Potentials↗

Deterioration of spinal reflex in quails orally ingesting clioquinol.

Ataxia occurred in quails on long-term oral ingestion of clioquinol (CQ). Crossed extensor reflexes and spinal reflex potentials in the normal and the treated quails were recorded. The incidence of these reflexes was reduced in quails given CQ. As long as the spinal reflexes were detected, there were no prominent differences in the profiles of the reflex potentials between the normal groups and those with ataxia. Augmentation of the reflex potentials by strychnine in the treated group was more extensive than that in the normal group. The mechanisms of action by which CQ induces ataxia are discussed.

Animals↗

The afferent and efferent pathways of the recto-colonic reflex in the dog.

The nature of the afferent and efferent pathways of the recto-colonic reflex was studied electrophysiologically in the dog. A compound action potential consisting of many peaks was evoked on a sacral dorsal rootlet by a stimulus to the ipsilateral rectal strands of the pelvic nerve. Conduction velocities of the peaks indicate that A delta and C afferent fibers innervate the colon and rectum. When the stimuli were subthreshold for C fibers, the reflex discharges of contralateral parasympathetic post-ganglionic fibers in the rectal strands and the reflex contraction of the colon were smaller than those caused by stronger stimuli. As the intensity of the stimulus to the sacral ventral roots was weakened, response peaks of preganglionic B fibers in the rectal branch, post-ganglionic C fibers in the rectal strands and a bladder branch of the pelvic nerve disappeared in the order of slow to fast conduction velocities. Contraction of the colon also decreased. The number of peaks arising from each nerve correlated well with the strength of the contraction. These results indicate that the peripheral limbs of the recto-colonic reflex arc consist of afferent A delta and C fibers, preganglionic B fibers and post-ganglionic C fibers.

Action Potentials↗

Lung tumor imaging by positron emission tomography using C-11 L-methionine.

This paper described the first clinical study of lung tumor scanning by positron emission tomography (PET) using C-11-labeled L-methionine (11C-L-Met). Tumor images were clearly visualized by high contrast in eight lung cancer patients and also in a patient with a silicotic nodule. Quantitative evaluations of methionine uptake in tumor tissue and normal tissue by comparing differential uptake ratios suggested that the extent to which 11C-L-Met accumulates in a tumor is closely correlated to the tumor's viability such as benign or malignant, viable or necrotic. 11C-L-Met is considered to be an effective tumor marker for PET diagnosis which represents increased amino acid metabolism of tumors in the mediastinum and lung.

Carbon Radioisotopes↗