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T Segawa

Publications and source records attributed to T Segawa.

At least 127 records · Page 7Linked to original sources
PubMed1986

Long-term lithium treatment causes serotonin receptor down-regulation via serotonergic presynapses in rat brain.

The effects of lithium treatment on serotonin (5-HT) receptors in rat frontal cortex and hippocampus were investigated. Long-term lithium treatment strongly blocked 5-hydroxytryptophan-induced head twitches, while acute lithium administration by itself induced head twitches in rats, and ketanserin blocked this acute lithium action. Long-term administration of lithium decreased the number of not only 5-HT2 receptors in the frontal cortex but also 5-HT1 and 5-HT2 receptors in the hippocampus in rats. Decreases in 3H-5-HT binding to hippocampal 5-HT1 receptors and 3H-spiperone binding to frontal cortical 5-HT2 receptors, caused by chronic lithium treatment, were abolished by co-administration of p-chlorophenylalanine, and were enhanced by co-administration with methiothepin. The turnover of 5-HT in either frontal cortex or hippocampus was facilitated by lithium, and co-administered methiothepin enhanced this facilitation. These results suggest that long-term lithium treatment causes the down-regulation of postsynaptic 5-HT1 and 5-HT2 receptors, in part probably through its action on presynaptic nerve terminals.

5-Hydroxytryptophan↗
PubMed1986

Fluid volume balance between pulmonary intravascular space and extravascular space in dogs.

We aimed to study the agreement of estimates of the pulmonary blood volume by the double indicator dilution method and the direct destructive method and the fluid volume balance between the pulmonary intravascular and extravascular spaces. We employed the double indicator dilution method using heat and indocyanine green, with a single injection (into the right atrium) and double sampling technique, that is from the pulmonary artery trunk (PAT) and the aortic root (Ao). With this method, we simultaneously determined the pulmonary extravascular water volume (PEWV), defined as the extravascular lung thermal volume estimated in Ao (LTVAo), and the pulmonary blood volume (PBV) from PAT to the left atrium (LA) (PBVPAT-LA). Dogs were divided into groups: a group without intervention (n = 16), a group loaded with dextran (n = 12) and a group loaded with alloxan (n = 7). When all groups were included, PBVPAT-LA (ml/kg) = 1.02 X PBVdirect(g/kg) + 0.96, n = 35, r = 0.83 where PBVdirect means the blood contents from the pulmonary artery bifurcation to the pulmonary vein measured by the direct destructive method. We substantiated the validity of the use of the double indicator dilution method. In studying the fluid volume balance, based on the results of the direct destructive method, the pulmonary intravascular-extravascular fluid volume ratio (intra/extra) was 1.3 +/- 0.3 (mean +/- SD) in the control state, implying that the interstitium in the lung is relatively "dry". As overt pulmonary edema developed by dextran infusion, the ratio exponentially decreased to 1.0 +/- 0.1 (p less than 0.01). The behavior of the fluid volume balance in question (intra/extra), studied with the double indicator dilution method, was essentially similar to that analyzed by the direct destructive method.

Alloxan↗
PubMed1986

Comparison of effects of tiapride and sulpiride on D-1, D-2, D-3 and D-4 subtypes of dopamine receptors in rat striatal and bovine caudate nucleus membranes.

To determine the affinity of tiapride to D-1, D-2, D-3 and D-4 subtypes of dopamine (DA) receptors, inhibitory effects of tiapride on [3H]-cis-flupenthixol, [3H]spiperone and [3H]N-propylapomorphine binding were examined in the rat striatum and bovine caudate nucleus membranes and compared to those of sulpiride and haloperidol. The IC50 values of tiapride, sulpiride and haloperidol were estimated as follows: 1440, 132 and 0.295 microM for D-1; 45.8, 8.8 and 0.004 microM for D-2; greater than 100, greater than 100 and 0.64 microM for D-3; 11.7, 2.88 and 0.0044 microM for D-4, respectively. It is suggested that the affinity of tiapride is high to D-2 and D-4, but is not high to D-1 and D-3. The affinity pattern of tiapride to each DA receptor subtype is similar to but lower than those of sulpiride and haloperidol. In the D-2 receptor assay, the IC50 values of tiapride and sulpiride were 1/22.7 and 1/19.1 of those in the presence of 100 mM NaCl, respectively, suggesting that benzamide drug binds to the D-2 subtype with higher affinity in the presence of Na+ than in the control.

Animals↗
PubMed1985

Decrease of clonidine binding affinity to alpha 2-adrenoceptor by ADP-ribosylation of 41,000-dalton proteins in rat cerebral cortical membranes by islet-activating protein.

The IC50 value for inhibition of specific [3H]yohimbine binding to rat cerebral cortical membranes by clonidine was increased, and the Hill coefficient (nH) approached unity in the presence of 150 microM GTP. Pretreatment of membranes with islet-activating protein (IAP) in the presence of NAD caused an increase in IC50 and nH values for clonidine compared with control membranes in the absence of GTP, the addition of which was without effect. Scatchard analysis showed that the Bmax value of the high-affinity component in [3H]clonidine binding was decreased by pretreatment with IAP/NAD. GTP in a concentration range of 0.1 microM-1 mM caused a significant elevation of [3H]yohimbine binding. In IAP/NAD-pretreated membranes, however, [3H]yohimbine binding was no longer affected by GTP, although IAP/NAD significantly (p less than 0.01) increased [3H]yohimbine binding compared to control. IAP ADP-ribosylated 41,000 dalton proteins of cerebral cortical membranes. From these results, it can be suggested that inhibitory guanine nucleotide regulatory protein with Mr 41,000 couples to alpha 2-adrenoceptors to regulate binding affinity of agonists and antagonists in membranes of the rat cerebral cortex.

Adenosine Diphosphate Ribose↗
PubMed1985

Possible involvement of inhibitory GTP binding regulatory protein in alpha 2-adrenoceptor-mediated inhibition of adenylate cyclase activity in cerebral cortical membranes of rats.

Influences of alpha 2-adrenoceptor stimulation on adenylate cyclase activity were investigated in cerebral cortical membranes of rats. Pretreatment of the membranes with islet-activating protein and NAD resulted in a significant increase in basal activity as well as in GTP- or forskolin/GTP-induced elevation of adenylate cyclase activity. Strong activation of adenylate cyclase was also caused in membranes pretreated with cholera toxin together with NAD in comparison to that in control membranes, suggesting that adenylate cyclase activity is perhaps regulated by stimulatory and inhibitory GTP binding regulatory protein existing in synaptic membranes. In addition, adrenaline (with propranolol) or clonidine significantly reduced adenylate cyclase activity stimulated by pretreatment with forskolin and GTP. The inhibitory effects of adrenaline were also observed in membranes pretreated with cholera toxin and NAD. Moreover, the inhibition by adrenaline or clonidine was completely abolished by treatment with (a) yohimbine or (b) islet-activating protein and NAD. It is suggested that alpha 2-receptor stimulation causes inhibitory influences on adenylate cyclase activity mediated by the inhibitory GTP binding regulatory protein in synaptic membranes of rat cerebral cortex.

Adenylate Cyclase Toxin↗
PubMed1985

The active principles of the branchlet and hook of Uncaria sinensis Oliv. examined with a 5-hydroxytryptamine receptor binding assay.

Of the alkaloids obtained from Uncaria sinensis Oliv., geissoschizine methyl ether, corynantheine and dihydrocorynantheine decreased specific [3H]5-HT binding to membrane preparations from rat brain and from in-vitro experiments on guinea-pig ileum, these alkaloids were found to be partial agonists for 5-HT receptors. Therefore, they might be useful in the treatment of diseases resulting from disorders of 5-HT metabolism.

Alkaloids↗
PubMed1985

[Dopamine-induced up-regulation of alpha 2-adrenoceptors in crude synaptic membranes of rat brain].

After cerebral cortical membranes were incubated with 0.1-100 microM of dopamine (DA) in 50 mM Tris-HCl buffer (pH 7.7) at 37 degrees C for 30 min, [3H] clonidine binding to alpha 2-receptors was increased in a concentration-dependent manner without changing [3H] WB4101 and [3H] DHA binding to alpha 1- and beta-receptors, respectively. Scatchard analysis of [3H] clonidine binding to cortical membranes showed that DA increased the Bmax in both high- and low-affinity components. The increasing effect of DA on [3H] clonidine was dependent on incubation time and temperature, and it was antagonized by pimozide and cis-flupenthixol. The addition of GTP produced a reduction in DA-induced elevation in [3H] clonidine binding, while that of cyclic AMP did not affect the effect of DA. DA and Mn2+, though both of them increased [3H] clonidine binding, appeared to act at a different site in the membrane. Furthermore, the DA-induced increase in [3H] clonidine was found uniformly in membranes prepared from 7 other regions of the rat brain. These results suggested that DA regulates specifically alpha 2-receptor density by stimulating D1-receptors and/or via other mechanism(s).

Animals↗
PubMed1985

[Double indicator dilution method using heat and dye to measure pulmonary extravascular water volume].

It is widely accepted that extravascular lung thermal volume estimated by the double indicator dilution method with heat as a diffusible indicator reliably reflects pulmonary extravascular water volume. Theoretically, as a premise, the indicator should be preserved during its pulmonary circulation. We therefore investigated the thermal conservation during pulmonary circulation; that is, whether there was good agreement in the cardiac outputs "wherever" the thermodilution curves were recorded; for instance, the pulmonary artery trunk (PAT), giving COPAT,heat and the aortic root (Ao), giving COAo,heat. In the present study, we observed a total of 59 pairs of cardiac outputs in dogs (n = 13), including dogs with overt pulmonary edema, produced either by dextran infusion or by alloxan administration. We also studied a total of 23 pairs of cardiac outputs of human subjects (n = 16) with ischemic heart disease or mild mitral stenosis. A mixture of ice-cold 5% glucose solution and indocyanine green was rapidly injected into the right atrium. The thermodilution curve was immediately recorded in the pulmonary artery trunk, and the thermodilution and dye dilution curves were recorded in the aorta using a conventional Swan-Ganz catheter. The cardiac outputs were calculated manually following the Stewart-Hamilton principle. The results were as follows: In dogs, COPAT,heat averaged 2.47 +/- 1.21 L/min (mean +/- SD), COAo,heat averaged 2.44 +/- 1.12 L/min and the difference was not significant (0.3 less than p less than 0.5). The regression equation was COPAT,heat = 1.01 X COAo,heat + 0.02 (n = 59, r = 0.93, p less than 0.001) and the correlation coefficient was excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of a fluorinated pyrimidinedione anti-cancer drug, 5-fluoro-1-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (FT), and related compounds on nigro-striatal dopaminergic neurons in the central nervous system.

The cause of the side effects of 5-fluoro-1-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (FT) on the central nervous system (CNS), and especially the extrapyramidal system were investigated by examining the effects of FT on pre- and post-synaptic functions of the dopaminergic system in comparison with the effects of 5-fluoro-2,4-pyrimidinedione (5-FU) and UFT. FT caused a significant decrease of spontaneous motor activity (SMA), significant increases in the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), an increase in dopamine (DA) turnover induced by alpha-methyl-p-tyrosine and an inhibition of presynaptic dopamine receptors. FT also slightly inhibited [3H] spiperone binding to rat striatal membranes (10-15%) in vitro at doses of 10(-6)-5 X 10(-4) M. 5-FU slightly decreased SMA, significantly increased the levels of DOPAC and HVA, and significantly inhibited (P less than 0.05) [3H]spiperone binding (about 30% at 5 X 10(-4) M). The effects of UFT on the CNS were almost the same as those of FT, but uracil had no effect on the CNS. These results suggest that the side effects of FT on the CNS, especially its action on dopaminergic neurons, may result from blockade of pre- and post-synaptic dopamine receptors, and may be mediated by its main metabolite 5-FU in the brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Studies on peptides. CXXVIII. Application of new heterobifunctional crosslinking reagents for the preparation of neurokinin (A and B)-BSA (bovine serum albumin) conjugates.

A decapeptide corresponding to the entire amino acid sequence of neurokinin A, a porcine spinal cord peptide, was synthesized in a conventional manner using protecting groups removable by 1 M TFMSA-thioanisole in TFA. The HS-CH2CH2CO group was introduced onto the synthetic neurokinin A by reaction of 3-(S-acetyl-thiopropionyl)-thiazolidine-2-thione, followed by deacetylation with hydroxylamine. 2,4-Dinitrophenyl-p-(beta-nitrovinyl)-benzoate trapped the above HS-CH2CH2CO-neurokinin A derivative in acidic media, then BSA in basic media in nearly quantitative yield. A similar decapeptide, neurokinin B, was also synthesized and conjugated onto BSA using an alternative SH-introducing reagent, 3-(S-p-methoxybenzyl-thiopropionyl)-thiazolidine-2-thione, and the above heterobifunctional conjugating reagent.

Amino Acid Sequence↗
PubMed1984

Activation of adenylate cyclase by dopamine, GTP, NaF and forskolin in striatal membranes of neonatal, adult and senescent rats.

Dopamine (DA) caused a significant activation of striatal adenylate cyclase in neonatal and adult but not in senescent rats. GTP activated cyclase at the adult stage but not at both neonatal and senescent stages. NaF and forskolin activated cyclase at every stage. The coupling mechanism between DA1 receptors and catalytic units of cyclase seems to become functional at the neonatal stage but GTP recognition and/or binding sites lack in stimulatory GTP binding protein in neonatal and senescent membranes.

Adenylyl Cyclases↗
PubMed1984

The interaction between beta- and alpha 2-adrenoceptors in cerebral cortical membranes: isoproterenol-induced increase in [3H]clonidine binding in rats.

The pretreatment of rat cerebral cortical membranes with 10 or 100 microM isoproterenol at 37 degrees C for 40 min caused a significant elevation of the Bmax value of [3H]clonidine binding but pretreatment at 4 degrees C did not affect the value. The isoproterenol-induced increase in the Bmax value of the binding was higher in 50 mM Tris-HCl buffer (pH 7.7) than in Krebs-Ringer solution. In 50 mM Tris-HCl buffer (pH 7.7), treatment with isoproterenol reduced the Bmax value of [3H]dihydroalprenolol binding but neither Kd nor Bmax of [3H]WB 4101 binding was affected by this treatment. Fifty microM propranolol or 100 microM GTP produced a significant reduction in isoproterenol-induced elevation of the Bmax value of [3H]clonidine binding. In contrast, 100 microM cyclic AMP did not affect the control binding and 0.1 or 1 mM theophylline did not affect the isoproterenol-induced elevation of the binding. The only Bmax value in high affinity binding of [3H]clonidine was increased by isoproterenol. It is suggested that isoproterenol increases the density of alpha 2-adrenoceptors in a temperature-dependent manner. The direct interaction between beta- and alpha 2-receptor molecules and/or their indirect interaction, mediated by GTP regulatory proteins, would exist in the cerebral cortical membranes of rats.

Animals↗