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Biomedical subjects

T Segawa

Publications and source records attributed to T Segawa.

At least 163 records · Page 9Linked to original sources
PubMed1982

Alteration in sensitivity to isoproterenol and acetylcholine in the rat heart after repeated administration of isoproterenol.

Alteration of sensitivity to the inotropic responses to isoproterenol and acetylcholine (ACh) and of saturation constants for the specific binding of [3H]dihydroalprenolol and [3H]quinuclidinyl benzilate to particulate fractions were investigated in rat hearts chronically treated with isoproterenol. The EC50 value for the inotropic response to isoproterenol in the atria of rats injected i.p. with isoproterenol (0.01 or 0.1 mg/kg) twice a day for 10 days, was 9.0-fold higher than in controls. Isoproterenol (0.17 mg/kg i.p.)-induced stimulation of cardiac ornithine decarboxylase activity was significantly (P less than .05) attenuated in atria from animals of the treated groups. Scatchard analysis of specific binding of [3H]dihydroalprenolol revealed that repeated isoproterenol injection produced a significant decrease in the maximum number of binding sites (Bmax), but not in the dissociation constant (KD) for this antagonist. In comparison to the isoproterenol-induced changes in beta adrenergic positive inotropic response, repeated treatment with isoproterenol decreased 2-fold the EC50 value for the negative inotropic response to ACh in isolated atria. Scatchard analysis of specific [3H]quinuclidinyl benzilate binding, however, indicated a significant (P less than .01) decrease in Bmax. Repeated isoproterenol injections also elicited a significant increase in cardiac weight. It is suggested that repeated administration of isoproterenol induces a decrease in density of beta adrenergic receptors which may in part underlie a cardiac hyposensitivity to isoproterenol and an increase in the number of muscarinic ACh receptors and inotropic responsiveness to ACh.

Acetylcholine↗
PubMed1981

Kinetic correlations between the disulfide bond reduction and the induced conformational change of proteins.

Kinetic correlations between the disulfide bond reduction in excess dithioerythritol and the induced conformational change were studied on two proteins, bovine alpha-lactalbumin and soybean trypsin inhibitor, at 25 degrees C and pH 8.0-8.5 by measuring the absorbance of oxidized dithioerythritol at 310 nm and the ellipticity at 270 nm, respectively. With alpha-lactalbumin, in the absence of guanidine hydrochloride (Gdn x HCl) or in dilute Gdn x HCl, the kinetics for the bond reduction and the conformational change were both of a biphasic type. The fast phase was complete within a few seconds and was associated with the reduction of some of the disulfide bonds and with almost complete loss of the tertiary structure. The slow phase was associated with the reduction of other disulfide bonds. In concentrated Gdn x HCl, the kinetics of both processes were observed as a single phase, the rate of which was similar to that of the slow phase in the absence of Gdn x HCl or in dilute Gdn x HCl. In all cases studied, the rate of the bond reduction was similar to that of the conformational change induced. By correcting the change in absorbance at 310 nm to a contribution from the protein due to the conformational change, the number of bonds which are reduced in the fast phase in the absence of Gdn x HCl was determined to be 1.0-1.1. It was shown, taking observations of others and theoretical results into account, that the bond reduced in the fast phase might be the one between Cys 6 and Cys 120. On the other hand, on of two bonds of soybean trypsin inhibitor in the native form was reduced in the fast phase without any loss of the tertiary structure, and the other was reduced in the slow phase. Considering the results of other researchers, it was concluded that the bond reduced in the fast phase of the inhibitor is a 136-145 bond.

Animals↗
PubMed1981

Comparison of synaptosomal and glial uptake of pipecolic acid and GABA in rat brain.

The active uptake of [3H]pipecolic acid increased with incubation time and its uptake at 3 min was half of that at 20 min. On the other hand, a ratio (pellet/medium) of [3H]pipecolic acid uptake into glial cell-enriched fractions, was much less (0.4 - 0.6) than that of [14C]GABA (25.8 - 74.1). GABA, 10(-4) M, and pipecolic acid, 10(-4) M, produced a significant inhibitor of [3H]pipecolic acid uptake into P2 fractions. Pipecolic acid, 10(-4) M, significantly reduced the synaptosomal and glial uptake of [14C]GABA. GABA, 10(-4) M, affected neither spontaneous nor high K+-induced release of [3H]pipecolic acid from brain slices. It is suggested that pipecolic acid is involved in either synaptic transmission or in its modulation at GABA synapses in the central nervous system.

Animals↗
PubMed1981

Ontogenetic development of high potassium- and acetylcholine-induced release of dopamine from striatal slices of the rat.

The high K+- and acetylcholine (ACh)-induced release of [3H]dopamine (DA) were investigated in whole brain slices of fetuses and striatal slices of postnatal rats. A high K+-induced, Ca2+-dependent release of [3H]DA was demonstrated in brain on day 18 of gestation and the amount of release from the striatum increased during postnatal development. ACh induced [3H]DA release in striatal slices from 3-, 7- and 70-day-old rats but not from 1-day-old animals. ACh-induced [3H]DA release on both day 7 and day 70 was dependent on Ca2+ and significantly reduced by the addition of 5 x 10(-6) M atropine or 10(-5) M hexamethonium. It is suggested that DA is taken up into functionally releasable pools at a late fetal stage and that from around 3 days after birth, ACh may begin to regulate DA release by stimulating muscarinic and/or nicotinic receptors located on DA nerve terminals in the striatum.

Acetylcholine↗
PubMed1981

Active uptake of substance P carboxy-terminal heptapeptide (5-11) into rat brain and rabbit spinal cord slices.

We previously reported that nerve terminals and glial cells lack an active uptake system capable of terminating transmitter action of substance P (SP). In the present study, we demonstrated the existence of an active uptake system for SP carboxy-terminal heptapeptide, (5-11)SP. When the slices from either rat brain or rabbit spinal cord were incubated with [3H](5-11)SP, the uptake of (5-11)SP into slices was observed. The uptake system has the properties of an active transport mechanism: it is dependent on temperature and sensitive to hypoosmotic treatment and is inhibited by ouabain and dinitrophenol (DNP). In the brain, (5-11)SP was accumulated by means of a high-affinity and a low-affinity uptake system. The Km and the Vmax values for the high-affinity system were 4.20 x 10(-8) M and 7.59 fmol/10 mg wet weight/min, respectively, whereas these values for the low-affinity system were 1.00 x 10(-6) M and 100 fmol/10 mg wet weight/min, respectively. In the spinal cord, there was only one uptake system, with a Km value of 2.16 x 10(-7) M and Vmax value of 26.2 fmol/10 mg wet weight/min. These results suggest that when SP is released from nerve terminals, it is hydrolysed into (5-11)SP before or after acting as a neurotransmitter, which is in turn accumulated into nerve terminals. Therefore, the uptake system may represent a possible mechanism for the inactivation of SP.

Animals↗
PubMed1980

Hypersensitivity of cardiac beta-adrenergic receptors after neonatal treatment of rats with 6-hydroxydopa.

The cardiac beta-adrenergic response to noradrenaline (NA) was investigated in the rat neonatally s.c. treated with 6-hydroxydopa (6-OHDOPA, 75 mg/kg, 0, 2 and 4 days after birth). 6-OHDOPA treatment significantly (P < 0.05) reduced the NA content by 32% of the control in whole heart and markedly potentiated the isoproterenol (0.17 mg/kg, i.p.)-induced stimulation of ornithine decarboxylase activity which had been blocked by a preceding i.p. injection of propranol (10 mg/kg) at the adult stage. Scatchard analysis of the specific [3H]-dihydroalprenolol ([3H]DHA0 binding indicated that 6-OHDOPA induced an increase in the maximum number of specific binding sites of [3H]DHA but did not alter the dissociation constant. In addition, 6-OHDOPA treatment resulted in a potentiation of the positive inotropic response to NA but not to isoproterenol in isolated atria. It is suggested that 6-OHDOPA treatment produces an increased density of beta-adrenergic receptor sites relevant to the hypersensitivity of beta-receptors to NA.

Animals↗
PubMed1980

The enzymes of the galactose cluster in Saccharomyces cerevisiae. II. Purification and characterization of uridine diphosphoglucose 4-epimerase.

Uridine diphosphoglucose 4-epimerase (EC 5.1.3.2) of Saccharomyces cerevisiae was purified to homogeneity with a yield of 30%. The purification procedure involved ammonium sulfate precipitation, streptomycin treatment, chromatography on diethylaminoethyl cellulose and hydroxylapatite, and Bio-Gel A-0.5m gel filtration. With the purified enzyme preparation, Km and Vmax values for uridine diphosphogalactose were determined and found to be 0.22 mM and 1.26 mmol/h/mg of protein, respectively. The value of Vmax corresponds to a turnover rate of 3890 molecules of uridine diphosphogalactose converted to uridine diphosphoglucose/min/enzyme molecule. The pH optimum of the enzyme was found to be between 6.8 and 8.0. Amino acid analysis was carried out on the final preparation. Based on the result, the partial specific volume was calculated to be 0.74 ml/g. The NH2-terminal residue of the enzyme was studied by two different methods and found to be threonine. The molecular weight and subunit composition were determined by the combination of the sucrose density gradient centrifugation and gel filtration under nondissociating conditions, and by polyacrylamide gel electrophoresis under dissociating conditions. The results indicated that the enzyme has a molecular weight of 183,000, consisting of two identical subunits. Each molecule of the native enzyme contained 1 molecule of NAD+.

Amino Acids↗
PubMed1980

Further characterization of the binding of substance P to a fraction from rabbit brain enriched in synaptic membranes.

1. The present experiments were designed to further characterize the specific [3H]substance P (SP) binding to membrane fractions from rabbit brain. 2. The specific binding was resistant to treatment with proteolytic enzymes whereas phospholipase A(0.7 unit/ml), C(0.025 unit/ml) and D(6.2 unit/ml) reduced the specific binding without decreasing total binding. Neuraminidase (0.01 unit/ml) decreased total binding as well as the specific binding. 3. High concentration of Triton X-100 reduced the specific binding whereas deoxycholate, at 0.05%, reduced both total and the specific binding. 4. Na+ (50--200 mM) reduced the specific binding, depending on the concentrations employed, whereas K+ decreased the specific binding at 10 and 100 mM. The binding was reduced considerably by 100 mmol/l of CaCl2. 5. From these results it is suggested that the specific [3H]SP binding sites in membrane fractions from rabbit brain could be phospholipids.

Animals↗
PubMed1980

Pharmacological characterization of central alpha-adrenoceptors which mediate clonidine-induced locomotor hypoactivity in the developing rat.

The present experiment was designed to pharmacologically characterize receptors which mediate the clonidine-induced locomotor change in the developing rat. A subcutaneous injection of clonidine (0.78 mumol/kg) produced locomotor hyperactivity in 7-day-old rats but hypoactivity in 20-day-old rats. Phenoxybenzamine (1.5 mumol/kg, 5.9 mumol/kg and 15 mumol/kg) decreased spontaneous activity in a dose-dependent manner but did not antagonize clonidine-induced hypoactivity in 20-day-old rats. By contrast, the significant reversal of the clonidine-induced hypoactivity by pretreatment with phentolamine (1.6 mumol/kg and 6.3 mumol/kg), yohimbine (1.3 mumol/kg and 5.1 mumol/kg) and piperoxan (7.4 mumol/kg) was observed at such doses when the blockers did not cause any hypoactivity by themselves. It is suggested that clonidine could induce locomotor hypoactivity by activating presynaptic (alpha 2-type) alpha-adrenoceptors in the CNS of 20-day-old rat.

Aging↗
PubMed1980

Apomorphine- and haloperidol-induced change in 3,4-dihydroxyphenylacetic acid content in the mesolimbic-striatum of the developing rat.

The mesolimbic-striatal content of 3,4-dihydroxyphenylacetic acid (DOPAC) gradually increased with age in the developing rat. An intraperitoneal (i.p.) injection of apomorphine (2 mg/kg) or haloperidol (0.1 mg/kg) caused a significant change in the DOPAC content on day 20 and day 70, but not on day 7. However, a higher dose of apomorphine (10 mg/kg, i.p.) or haloperidol (5 mg/kg, i.p.) as well as that of alpha-flupenthixol (0.5 mg/kg, i.p.) significantly affected the mesolimbic-striatal content of DOPAC in 7-day-old rats. In 24-day-old rats subchronically treated with haloperidol (1 mg/kg to 10 mg/kg for 10 days, s.c.), apomorphine (2 mg/kg, i.p.) produced a significant reduction in the mesolimbic content of DOPAC at the withdrawal stage of the drug, but not in control rats. It is suggested that mesolimbic-striatal dopamine (DA) receptors which are not fully sensitive to DA agonists and antagonists on day 7 reach functional maturity by 20 days of the postnatal age in the rat.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

Ontogenesis of rearing and stereotypy responses to apomorphine in the rat.

The ontogenesis of rearing and stereotype behavior in response to apomorphine were investigated in the developing rat. The rearing was rarely observed in 15-day-old rats but distinctly in 18-day-old ones. A subcutaneous injection of apomorphine in dose of 1 mg/kg or 2 mg/kg decreased the frequency of rearing in older animals than day 20. On the other hand, 15-day-old rats were already responsive to apomorphine in stereotypy behavior. There was a reciprocal relationship between rearing and stereotypy responses to apomorphine in rat older than 18 days. Functional relationship between rearing and stereotypy in response to apomorphine were discussed in view of the central dopaminergic mechanisms in developing rats.

Age Factors↗