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Biomedical subjects

T Totsuka

Publications and source records attributed to T Totsuka.

At least 73 records · Page 4Linked to original sources
PubMed1987

Beta 1-adrenergic selectivity of the new cardiotonic agent denopamine in its stimulating effects on adenylate cyclase.

Effects of the new selectively beta 1-adrenergic cardiotonic drug denopamine (TA-064), (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol, on the adenylate cyclase-adenosine-3',5'-monophosphate (c-AMP) system of various tissues and cells in rats and guinea pigs were investigated in comparison with those of isoproterenol. Denopamine at concentrations above 10(-6) M stimulated lipolysis in vitro, and, above 10(-5) M, elevated the c-AMP level in isolated rat fat cells. The c-AMP level of guinea-pig heart ventricular muscle was also elevated when the heart was perfused with 3 X 10(-6) M denopamine or when slices of ventricular muscle were incubated with 10(-6) M denopamine. These changes were abolished in the presence of beta-adrenergic antagonists. Incubation with denopamine did not cause substantial elevation of c-AMP levels in rat reticulocytes and diaphragm. Denopamine activated adenylate cyclase of the rat cell membranes in a concentration-dependent manner. Although dose dependence was less apparent, denopamine also activated adenylate cyclase of the membrane fraction from guinea pig cardiac muscle, but it hardly activated the same enzyme from rat reticulocytes. Isoproterenol, on the other hand, showed marked concentration-dependent activation of adenylate cyclase in all these preparations. Denopamine did not inhibit c-AMP phosphodiesterase of both particulate and supernatant fractions of guinea-pig cardiac muscle. The stimulation of lipolysis by denopamine was observed even when elevation of the c-AMP level was not detected, while the stimulation of lipolysis by isoproterenol was always accompanied with an elevation of c-AMP. When guinea-pig hearts were perfused with 3 X 10(-6) M denopamine or 10(-7) M isoproterenol, their cardiotonic effects were of the same magnitude whereas the degree of c-AMP elevation in the ventricular tissue by denopamine was significantly less than that by isoproterenol. It was concluded that stimulation of the adenylate cyclase-c-AMP system by denopamine was restricted to the tissues whose receptors were predominantly of the beta 1-type, and that the elevation of c-AMP levels in these tissues by denopamine was less marked than by isoproterenol, suggesting that the stimulation of lipolysis and heart by denopamine may be mediated by a special pool of c-AMP or some other unknown factor(s).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Mechanical properties and ATPase activity in glycerinated cardiac muscle of hyperthyroid rabbit.

Isometric tension, tension transients in response to rapid step stretches in length and ATPase activity were measured at constant levels of various Ca2+ activations in glycerinated right ventricular papillary muscle of L-thyroxine-treated (14 daily injections of 0.2 mg/kg) and control rabbits. The isometric tension increased sigmoidally as Ca2+ was varied from slightly below pCa 7 to about pCa 6 both in thyroxine-treated and control preparations. The maximum isometric tension in thyroxine-treated preparations, however, was only about 66% of that in control. The tension transients were characterized by clear three distinct phases; the first phase of an immediate tension increase coincident with the stretch, the second phase of a rapid quasi-exponential tension decrease and the third phase of a delayed quasi-exponential tension rise. In thyroxine-treated preparations, relative to controls, the time for 63% tension reduction in the second phase decreased from 39.3 +/- 2.8 ms (mean +/- SD, n = 5) to 20.2 +/- 2.0 ms (p less than 0.001) and the time for 63% tension rise in the third phase decreased from 483.9 +/- 14.3 ms to 298 +/- 15.9 ms (p less than 0.001). The ATPase activity increased in a sigmoid fashion with increasing Ca2+ from slightly above pCa 7 to slightly below pCa 6 both in thyroxine-treated and control preparations. However, the tension cost (ATPase activity/tension) was about two times greater in the thyroxine-treated preparations than in controls.

Adenosine Triphosphatases↗
PubMed1986

Length-tension relation of cat heart muscle studied by a segment-control method.

We studied the effects of the damaged ends on the length-tension relationship of the cat right ventricular papillary muscle during twitch contraction (30/min) using a newly developed segment-control system. The segment length (SL), defined as the distance between two thin black films attached to the central surface of the muscle with silicone grease, was measured by a Hamamatsu Photonics Width Analyzer (C1170) and Camera (C1000) and controlled with a servoactuator. The marker distance was determined to be either the central 24%-30% (short marker distance) or 47%-56% (long marker distance) of the muscle length (ML) at which the maximum developed twitch tension was observed (MLmax). The muscle was lengthened and shortened in a triangular fashion under both ML and SL isometric twitch modes over a period of 250s. The relationship between ML or SL and developed tension (DT, total minus resting tension) was obtained from the twitch tension data during the lengthening. The DT in the SL isometric twitch was always greater than that in the ML isometric twitch over the range of lengths studied. The slope of the SL-DT relation curve was much less steep than that of the ascending limb of the ML-DT relation curve. The gradient of the SL-DT relationship curve was greater for the long marker than for the short marker distance. The percentage shortening of SL in the ML isometric twitch increased with decreasing ML; it was greater for the short marker than for the long marker distance, particularly at shorter MLs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Age-related changes in the content and composition of glycosaminoglycans isolated from the mouse skeletal muscle: normal and dystrophic conditions.

Glycosaminoglycans were isolated from the skeletal muscle of either normal or dystrophic mice aged from 3 to 18 weeks. The glycosaminoglycan content of the normal muscle, based on the tissue weight, decreased slightly during the period from 3 to 10 weeks, and remained almost unchanged after 10 weeks. The major glycosaminoglycan in normal muscle was hyaluronate, the relative amount of which increased slightly (from 70% to 80%) with age. Both dermatan sulfate and heparan sulfate were also obtained. The relative amounts of these sulfated glycosaminoglycans tended to decrease with age. On the other hand, the glycosaminoglycan content of the dystrophic muscle was higher than that of normal muscle even at 3 weeks. The proportion of hyaluronate was almost constant (about 65%) throughout the age range examined. The relative amount of dermatan sulfate increased from 20% to 30% with a compensatory decrease in the amount of heparan sulfate. Further, the incorporation of [35S]sulfate into glycosaminoglycans by the dystrophic muscle was reduced to about 60% of the normal. These differences in glycosaminoglycan composition and [35S]sulfate incorporation between the normal and the dystrophic muscles may be related to the progressive muscular dysfunction seen in this disease.

Aging↗
PubMed1985

Patterns of soleus muscle potentials to repetitive stimulation in young and aged rats.

Muscle potentials were recorded in the soleus muscle of Wistar rats anesthetized with urethane or Nembutal. The time course of their changes induced by repetitive stimulation of sciatic nerves at 5 Hz for 10 min was compared for young and aged rats. When stimulation commenced, muscle potentials from young rats were somewhat facilitated, followed by slight depression below control values, and thereafter they were gradually potentiated. On the contrary, muscle potentials from aged rats were rapidly reduced, attaining plateau levels 2 min or so after the onset of repetitive stimulation at 5 Hz.

Age Factors↗
PubMed1984

Effects of (-)-(R)-1-(p-hydroxyphenyl)-2-[3,4-dimethoxyphenethyl)amino]ethanol (TA-064), a new cardiotonic agent, on circulating parameters of carbohydrate and lipid metabolism in the rat.

Effects of the new cardiotonic and selective beta 1-adrenergic agonist TA-064, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino] ethanol, on circulating concentrations of glucose, lactate, free fatty acids (FFA), glycerol, cyclic AMP and the pancreatic hormones insulin (IRI) and glucagon (IRG) were examined in rats. TA-064, administered orally or intraperitoneally at the dose of 10 mg/kg (ca. 50 times the therapeutic dose) or higher, caused a slight transient rise followed by a persistent lowering of blood glucose concentrations, but it did not affect blood lactate levels at all. The same treatment with TA-064 elevated the concentrations of blood FFA, glycerol and plasma IRI and IRG. These changes induced by TA-064 were inhibited by pretreatment with propranolol (a non-selective beta-adrenergic antagonist) and practolol (a selective beta 1-adrenergic antagonist). The non-selective beta-adrenergic agonist isoproterenol and the selective beta 2-adrenergic agonist terbutaline elevated both blood glucose and lactate when administered intraperitoneally. They also brought about sustained rises in blood glycerol and plasma IRI, but only transiently increased the plasma IRG level. The cardiotonic agent prenalterol, claimed to be a selective beta 1-agonist, elevated blood glucose, lactate, and glycerol only slightly, and plasma IRI significantly, but it had no effect on plasma IRG. The cardiotonic agents dobutamine and amrinone also elevated blood glucose. Thus, TA-064 is unique among the beta-adrenergic and other cardiotonic agents in that it produces sustained hypoglycemia while it has no lactacidemic effect. Since this hypoglycemic action of TA-064 was always preceded by a rise in plasma IRI and abolished in streptozotocin-diabetic rats, we conclude that increased secretion of pancreatic insulin and the lack of hyperglycemic action are responsible for the hypoglycemia by high doses of TA-064.

Adrenergic beta-Agonists↗
PubMed1984

Differences among dystrophic, dwarf, and their crossbred mice in the time course of changes in extracellular muscle action potentials induced by 5-Hz stimulation.

With urethane anesthesia, extracellular action potentials were recorded in medial gastrocnemius muscles of dystrophic, dwarf, and their crossbred mice. When repetitive stimulation was delivered at 5 Hz for a relatively long period, characteristic features were revealed. (i) Dystrophic mice showed a slight decrease or even an increase in action potentials whereas in littermate normal mice the amplitudes were rapidly and notably reduced. (ii) In both dwarf and their littermate normal mice, a considerable reduction in amplitude was observed. Slightly more depression was produced than in nondystrophic mice of a comparable age. (iii) Crossbred mice were in two classes. A rapid and notable reduction in the amplitude of muscle action potentials was observed in one class, and slight changes in the potentials were produced in another class showing dystrophy-specific symptoms.

Action Potentials↗
PubMed1984

Ontogenetic aspects of changes in muscular potentials at medial gastrocnemius muscles of dystrophic mice due to prolonged stimulation.

Changes in muscular potentials at medial gastrocnemius (MG) muscles induced by prolonged stimulation at 5 Hz were compared in dystrophic mice and their normal littermates at various ages. A rapid and notable reduction in the amplitude of muscular potentials at MG muscles was observed in normal mice. This was in contrast with a slight decrease or even an increase in the amplitude in dystrophic mice. The magnitude of reduction in normal mice increased with age, but in dystrophic mice where the change (a decrease or even an increase) was slight, it was similar in extent regardless of age. The slight change in dystrophic mice under the present regimen would be called a fatigue, resistant-like property, and this was discussed in conjunction with analogous properties observed in electrophysiological, histological and biochemical fields.

Animals↗
PubMed1983

Hypoglycemic activity of 1-alpha-(3,4-dimethoxyphenethylaminomethyl) -2-hydroxybenzylalcohol 1/2 fumarate (TA-078) in the mouse, rat and dog.

1-alpha-(3,4-Dimethoxyphenethylaminomethyl)-2-hydroxybenzylalcohol 1/2 fumarate (TA-078) is a new hypoglycemic agent structurally different from any existing hypoglycemic drug. It depresses the rise of blood glucose when it is orally administered to glucose-loaded mice, rats and beagle dogs at minimal doses of 1, 10 and 2.5 mg/kg, respectively. In contrast with tolbutamide, TA-078 hardly affected fasting blood glucose levels in rats and dogs and only weakly reduced fasting blood glucose levels in mice. Oral administration of TA-078 to KK mice also improved glucose tolerance, while no improvement was observed in streptozotocin-diabetic rats. TA-078 elevated plasma immunoreactive insulin (IRI) levels in mice and rats soon after its oral administration. In fasted rats, TA-078 caused only a transient increase in plasma IRI but did not affect plasma immunoreactive glucagon (IRG) levels in the early phase after its administration. On the other hand, tolbutamide induced a sustained increase in plasma IRI and a transient but marked decrease in plasma IRG. In perfused rat pancreas, TA-078 stimulated insulin secretion. The stimulation by 10 micrograms/ml TA-078 in the perfusion liquid required the presence of a normal concn (5.6 mM) of glucose, whereas the same concn of tolbutamide stimulated insulin release even at a low glucose concn (2.8 mM).

Animals↗
PubMed1983

Contrast of time courses of changes in muscular potentials to prolonged stimulation at 5 Hz in rat medial gastrocnemius and soleus muscles.

Time courses of changes in muscular potentials to repetitive stimulation at 5 Hz for 10 min were compared between rat medial gastrocnemius (MG) and soleus (SOL) muscles. Stimuli were applied to a sciatic nerve near the entrance of the MG and lateral gastrocnemius (LG) muscles and its exit segment from the LG to the SOL muscles. Muscular potentials were generally evoked in the form of a biphasic wave at the MG muscle and were always of a simple biphasic pattern at the SOL muscle. It was found that, due to prolonged stimulation, muscular potentials were rapidly and notably reduced in the MG muscle, whereas they were gradually facilitated in the SOL muscle. This contrast was similar to differences in the time course of changes in muscular potentials under these conditions in the MG muscle of dystrophic and littermate normal mice.

Animals↗
PubMed1982

Elevated free cholesterol content in hindleg muscle of the dystrophic mouse during a postnatal period form 2.1 to 30 weeks.

Age-related changes in phospholipid and free cholesterol contents of hindleg muscles from normal and dystrophic (C57BL/6J dy/dy) mice were investigated. Free cholesterol contents in liver, whole blood and brain of dystrophic mice at 3 weeks of age were also compared with the control. Free cholesterol content tended to increase in the liver of the dystrophic mouse. Free cholesterol content of dystrophic muscle was significantly higher than that of normal muscle at each age (2.1 to 30 weeks old), while phospholipid contents in dystrophic muscles were nearly equal to those of the normal in age from 4 to 20 weeks.

Age Factors↗
PubMed1982

Different time courses of reduction in muscular potentials to moderate frequency stimulation in dystrophic and normal mice.

Muscular potentials were evoked by electrical stimulation of sciatic nerves and recorded from gastrocnemius muscles in dystrophic and normal mice. When frequency of stimulation was accelerated from 0.5 to 5 per sec and continued, the potentials were depressed to a notable extent in normal mice, whereas only a slight decrease or even an increase in them was observed in dystrophic mice. Thus, a simple method has been developed to differentiate pre- and/or postjunctional properties for impulse transmission in dystrophic mice from those in normal mice.

Action Potentials↗
PubMed1981

Some evidence for concurrent involvement of the fore- and hindleg muscles in murine muscular dystrophy.

Endurance of the forelegs of the dystrophic mouse was found to be significantly less than that of the normal mouse as early as at 3 weeks of age. It decreased progressively with age although the forelegs seemed to function almost normally even after 2 months of age by which time the hindlegs became almost immobile. Thus, histological and biochemical studies to compare the fore- and hindleg muscles of the dystrophic mice were conducted. Morphological abnormalities similar to those observed in the hindleg muscle were also found in foreleg muscles of the young dystrophic mice. Their foreleg and hindleg muscles showed significantly higher hydroxyproline contents than those of the normal mice even at 2 weeks of age when clinical signs of the disease first became manifest in their hindlegs. The present findings appear to be the first evidence for concurrent involvement of the fore- and hindleg muscles in murine muscular dystrophy. This would raise an issue as to why forelegs with abnormal muscles can subserve somewhat normal function, whereas hindlegs with abnormal muscles can subserve somewhat function, whereas hindlegs in these adult dystrophic mice are immobile. This might yield clues to clarify the mechanism underlying the aggravation of the disease.

Animals↗