Biomedical subjects

Y Yoneda

Publications and source records attributed to Y Yoneda.

At least 19 recordsLinked to original sources

PubMed1992

Noninvasive detection of left ventricular diastolic dysfunction using M-mode echocardiography to assess left ventricular posterior wall kinetics in hypertrophic cardiomyopathy.

In patients with hypertrophic cardiomyopathy (HC), it is difficult to determine the severity of left ventricular (LV) diastolic dysfunction. Three different patterns of LV posterior wall motion were found by M-mode echocardiography in patients with HC, and the use of these patterns is proposed as a new noninvasive index of the severity of LV diastolic dysfunction. M-mode echocardiograms were recorded prospectively from 35 patients with HC, and the posterior wall motion pattern in late systole and early diastole was classified into the following 3 types: (1) normal motion (n = 9); (2) flat motion--flat motion from late systole to early diastole, followed by rapid backward movement (n = 13); and (3) downward motion--slow backward movement from late systole (n = 13). There were no differences in the severity or type of hypertrophy, LV systolic function and pulsed Doppler indexes of LV filling among these 3 groups. However, LV end-diastolic pressure was increased in the groups with flat (15 +/- 6 mm Hg) and downward (16 +/- 9 mm Hg) motion. Furthermore, the maximal rate of decrease in LV pressure (normal 1,450 +/- 300, flat 1,250 +/- 300 and downward 860 +/- 80 mm Hg/s) and the time constant of LV pressure reduction (normal 60 +/- 15, flat 70 +/- 25 and downward 101 +/- 34 ms) showed a stepwise deterioration from the normal to the flat and then to the downward motion groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1992

Ionotropic excitatory amino acid receptors in discrete brain regions of kindled rats.

A study was performed to examine the specific binding of excitatory amino acid (EAA) receptor subtypes in 5 brain regions of rats kindled from the amygdala or hippocampus, using extensively washed and Triton X-100-treated membranes. Seven days after the last amygdala kindled seizure, [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10- imine maleate ([3H]MK-801) binding, which labels N-methyl-D-aspartate (NMDA)-sensitive receptor-linked cation channels, decreased significantly only in the amygdala of kindled rats compared to that of controls under equilibrium assay conditions. There was no significant change in [3H]MK-801 binding in the amygdala or hippocampus 7 days after the last hippocampal kindled seizure, or 28 days after the last amygdala kindled seizure. Nor was there a significant change in NMDA-sensitive [3H]glutamate, strychnine-insensitive [3H]glycine, [3H]spermidine, [3H]kainate or [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) binding in any brain region 7 days after the last amygdala kindled seizure, or in the hippocampus 28 days after the last amygdala kindled seizure. These results indicate that [3H]MK-801 binding sites labeling NMDA-sensitive receptor-linked cation channels in the amygdala undergo downregulation only transiently, but that none of the subcomponents of the NMDA receptor macromolecular complex exhibit enduring changes at steady state following the completion of amygdala kindling.

Amygdala↗

PubMed1992

Presence of the binding of a variety of ligands related to ionotropic excitatory amino acid receptors in rat retina.

The binding of [3H]L-glutamic (Glu), [3H](+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic and [3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acids was detected in rat retinal membranes extensively washed and treated with a low concentration of Triton X-100, in addition to the binding of both [3H]glycine (Gly) and [3H]5,7-dichlorokynurenic acid. Furthermore, retinal membranes exhibited the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne in the presence of Glu, Gly and spermidine irrespective of the incubation period employed. Rat retina also contained the binding of [3H]kainic acid as well as the binding of [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid which was sensitive to potentiation by potassium thiocyanate. In addition, the binding of both [3H](+)-3-(hydroxyphenyl)-N-(l-propyl)piperidine and [3H]1,3-di-o-tolyl-guanidine was found in rat retinal membranes extensively washed but not treated with Triton X-100. These results give support for the proposal that the rodent retina contains subclasses of ionotropic brain excitatory amino acid receptors including the N-methyl-D-aspartate receptor ionophore complex as well as sigma sites.

Animals↗

PubMed1992

Escherichia coli RecA protein modified with a nuclear location signal binds to chromosomes in living mammalian cells.

We tried to make a well-characterized bacterial protein function in mammalian cell nuclei. For this purpose we chose Escherichia coli RecA protein and fused its carboxy terminus to the nuclear location signal of SV40 large T-antigen by oligonucleotide-dependent modification of the gene. When injected into the cytoplasm, the modified RecA protein (T-RecA for the T-antigen signal) accumulated efficiently in the nuclei, whereas the wild-type RecA protein remained in the cytoplasm. The T-RecA protein retained its original in vivo activity, judging from the finding that uv-sensitive bacteria (recA- E. coli) became uv-resistant on transformation with the T-recA plasmid as well as the recA plasmid. For expression of the T-recA gene in mammalian cells, the 5' region was replaced by the chicken beta-actin promoter and Kozak's initiation signal. A high level of expression was observed when Chinese hamster ovary (CHO-K1) cells were transfected with this plasmid. Indirect immunofluorescence examination revealed that the T-RecA protein in nuclei of mammalian cells bound to chromatin.

Amino Acid Sequence↗

PubMed1992

A long synthetic peptide containing a nuclear localization signal and its flanking sequences of SV40 T-antigen directs the transport of IgM into the nucleus efficiently.

Synthetic short peptides containing only the nuclear localization signal (NLS) direct the transport of nonnuclear proteins into the nucleus. As a conjugate of the synthetic peptide with immunoglobulin M (IgM) did not enter the nucleus, there was believed to be a size limit for nuclear transport of NLS-conjugated proteins. However, we found that IgM conjugated with purified nucleoplasmin, a nuclear protein of Xenopus oocytes, rapidly accumulated in the nucleus. For direct comparison with the short peptide, we prepared a long peptide containing the NLS and its flanking sequences of SV40 large T-antigen and its mutated long peptide, in which possible phosphorylation sites located at the amino terminal of the NLS were changed to alanine. Kinetic experiments showed that wild-type long peptide-IgM conjugates were almost entirely taken up into the nucleus within 30 min after their injection, whereas almost 60 min was required for the mutated long peptide-IgM conjugates to enter the nucleus of all the cells examined, and there was no apparent accumulation of short peptide-IgM conjugates in the nucleus within 60 min. These results indicate that even when the kinetics of transport are affected by amino acid substitutions, the long peptide directs the transport of large molecules such as IgM into the nucleus.

Amino Acid Sequence↗

PubMed1992

Effects of ifenprodil on the N-methyl-D-aspartate receptor ionophore complex in rat brain.

The effects of a cerebral anti-ischemic drug ifenprodil on the receptor ionophore complex of an N-methyl-D-aspartate (NMDA)-sensitive subclass of central excitatory amino acid receptors were examined using [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10- imine (MK-801) binding in rat brain synaptic membrane preparations as a biochemical measure. The binding in membrane preparations not extensively washed was markedly inhibited not only by competitive NMDA antagonists such as (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic, D-2-amino-5-phosphonovaleric and D-2-amino-7-phosphonoheptanoic acids, but also by competitive antagonists at the strychnine-insensitive glycine (Gly) site including 7-chlorokynurenic acid and 6,7-dichloroquinoxaline-2,3-dione. Among several proposed ligands for alpha-adrenergic receptors tested, ifenprodil most potently inhibited the binding in these membrane preparations due to a decrease in the density of the binding sites without significantly affecting the affinity. Ifenprodil also inhibited the binding of [3H]N-[1-(2-thienyl)cyclohexyl]piperidine as well as of [3H]MK-801 to open NMDA channels in a concentration-dependent manner at concentrations above 10 nM in membrane preparations extensively washed but not treated by a detergent, with a Hill coefficient of less than unity. Further treatment of extensively washed membrane preparations with a low concentration of Triton X-100 resulted in an almost complete abolition of [3H]MK-801 binding, and the binding was restored to the level found in membrane preparations not extensively washed following the addition of both L-glutamic acid (Glu) and Gly. Ifenprodil was effective in inhibiting [3H]MK-801 binding via reducing both initial association and dissociation rates in Triton-treated membrane preparations, irrespective of the presence of Glu and Gly added. The binding in Triton-treated membrane preparations was additionally potentiated by the polyamine spermidine in a concentration-dependent manner at concentrations above 10 microM in the presence of both Glu and Gly at maximally effective concentrations. Ifenprodil invariably diminished the abilities of these three stimulants to potentiate [3H]MK-801 binding at concentrations over 1 microM in a manner that the maximal responses each were reduced. These results suggest that ifenprodil does not interfere with the NMDA receptor complex as a specific isosteric antagonist at the polyamine domain in contrast to the prevailing view.

Adrenergic alpha-Antagonists↗

PubMed1992

Excitatory amino acid receptors in brains of rats with methylazoxymethanol-induced microencephaly.

We used methylazoxymethanol-acetate (MAM), a potent alkylating agent, to produce microencephaly in offspring by injecting it into pregnant rats on day 15 of gestation. Binding activities of central excitatory amino acid receptors were examined in Triton-treated membranes prepared from brains of adult offspring with MAM-induced microencephaly (MAM rats). MAM rats exhibited approximately 40-50% reductions of the wet weights of the cerebral cortex, hippocampus and striatum compared to those in controls. In the cortex and hippocampus of MAM-rats, total bindings of [3H]glutamate (Glu) (which is sensitive to N-methyl-D-aspartate (NMDA) receptor), and strychnine-insensitive [3H]glycine (Gly) and (+)-5-[3H]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801; a noncompetitive antagonist of NMDA receptor), were reduced to approximately 40% of those in controls. Similarly, in both regions of MAM rats, total bindings of [3H]kainate and DL-alpha-amino-3-[3H]hydroxy-5-methylisoxazole-4-propionic acid (an agonist of quisqualate receptors), were reduced to approximately 35-50% of those in controls. However, total bindings of these radioligands in the striatum of MAM rats were more than 65% of those in controls, despite the significant loss of striatum mass. However, specific bindings of radioligands in the striatum of MAM rats were elevated by more than 60% of those in controls, and Scatchard analysis revealed that elevations of [3H]Glu, [3H]Gly and [3H]MK-801 bindings were due to a significant increase in the densities of binding sites, with their affinities remaining unaltered. Spatial recognition ability examined by an 8-armed radial maze task was markedly impaired compared to those in controls. These results suggest that the proliferation of neurons bearing excitatory amino acid receptors (EAA) in the striatum is less affected by MAM treatment on day 15 of gestation than that in the cortex and hippocampus in spite of drastic weight loss in these brain regions. The significant reduction of EAA receptors in the cortex and hippocampus may be involved in the impairment of spatial memory observed in MAM-treated rats.

Animals↗

PubMed1992

Antibodies against 70-kD heat shock cognate protein inhibit mediated nuclear import of karyophilic proteins.

Previously, we found that anti-DDDED antibodies strongly inhibited in vivo nuclear transport of nuclear proteins and that these antibodies recognized a protein of 69 kD (p69) from rat liver nuclear envelopes that showed specific binding activities to the nuclear location sequences (NLSs) of nucleoplasmin and SV-40 large T-antigen. Here we identified this protein as the 70-kD heat shock cognate protein (hsc70) based on its mass, isoelectric point, cellular localization, and partial amino acid sequences. Competition studies indicated that the recombinant hsc70 expressed in Escherichia coli binds to transport competent SV-40 T-antigen NLS more strongly than to the point mutated transport incompetent mutant NLS. To investigate the possible involvement of hsc70 in nuclear transport, we examined the effect of anti-hsc70 rabbit antibodies on the nuclear accumulation of karyophilic proteins. When injected into the cytoplasm of tissue culture cells, anti-hsc70 strongly inhibited the nuclear import of nucleoplasmin, SV-40 T-antigen NLS bearing BSA and histone H1. In contrast, anti-hsc70 IgG did not prevent the diffusion of lysozyme or 17.4-kD FITC-dextran into the nuclei. After injection of these antibodies, cells continued RNA synthesis and were viable. These results indicate that hsc70 interacts with NLS-containing proteins in the cytoplasm before their nuclear import.

Amino Acid Sequence↗

PubMed1992

Decreased hypothalamic and medullary GABA turnover in spontaneously hypertensive rats.

OBJECTIVE: The aim was to assess whether Gamma-aminobutyric acid (GABA) neurone activities in the central nervous system, especially in the hypothalamus and medulla oblangata, are altered in hypertension. METHODS: Central GABA content and turnover rate were measured in spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls (WKY). GABA content was determined with high performance liquid chromatography, and in vivo GABA turnover rates were estimated by GABA accumulation after injection of amino-oxyacetic acid, a selective inhibitor of GABA degrading system. Two groups of nine week old male rats (32 SHR and 32 WKY) were used. RESULTS: GABA concentrations in cerebrospinal fluid were lower in SHR than in WKY. Since hypothalamus and medulla oblongata are the possible active sites of this system, basal GABA contents and in vivo GABA turnover rates were measured in hypothalamus and medulla oblongata. Basal GABA content in the medulla oblongata and hypothalamus was almost equal in SHR and WKY. On the other hand, GABA turnover rates were significantly lower in SHR than in WKY in both the hypothalamus and the medulla. CONCLUSIONS: Since it is known that GABA is an inhibitory neurotransmitter in the central nervous system and that it controls autonomic and cardiovascular activities, the findings suggest that the decreased hypothalamic and medullary GABAergic activities may permit sympathetic hyperactivity to contribute to the increase in blood pressure in SHR.

Aminooxyacetic Acid↗

PubMed1992

Inhibition by calmodulin antagonists of [3H]MK-801 binding in brain synaptic membranes.

In brain synaptic membranes not extensively washed, (+)-5-[3H]methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5, 10-imine ([3H]MK-801) binding was markedly inhibited in a concentration-dependent manner (at concentrations above 1 microM) by several compounds having antagonistic activity at the Ca(2+)-binding protein calmodulin. Scatchard analysis revealed that N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) inhibited the binding through a significant decrease in the density of binding sites without affecting the affinity at 10 microM. In membranes extensively washed and treated with a low concentration of Triton X-100, L-glutamic acid (Glu) drastically accelerated the initial association rate of [3H]MK-801 binding with glycine (Gly), almost doubling the initial association rate found in the presence of Glu alone. The addition of W-7 invariably reduced the initial association rate observed in the presence of either Glu alone or both Glu and Gly, without significantly altering the dissociation rate of bound [3H]-MK-801, irrespective of the presence of the two stimulatory amino acids. The maximal potencies of Glu, Gly, and spermidine in potentiating the binding were all attenuated by W-7. These results suggest that calmodulin antagonists may interfere with opening processes of an ion channel associated with an N-methyl-D-aspartate-sensitive subclass of excitatory amino acid receptors in rat brain.

Animals↗

PubMed1992

Differential modulation by divalent cations of [3H]MK-801 binding in brain synaptic membranes.

Endogenous divalent cations, such as Mg2+, Ca2+, and Zn2+, differentially affected the binding of (+)-[3H]5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate ([3H]MK-801) to an ion channel associated with an N-methyl-D-aspartate-sensitive subclass of excitatory amino acid receptors in different preparations of brain synaptic membranes. Both Mg2+ and Ca2+ were weak inhibitors of the binding in membranes which had not been extensively washed (nonwashed membranes), over a concentration range effective in markedly potentiating the binding in the absence of any added stimulants in membranes which had been extensively washed, but not treated with a detergent (untreated membranes). In membranes extensively washed and treated with Triton X-100 (Triton-treated membranes), both cations significantly potentiated the binding in the presence of added glutamate alone. In contrast, Zn2+ was invariably active as a potent inhibitor of the binding irrespective of the membrane preparations used. In untreated membranes, Ca2+ markedly accelerated the initial association rate of [3H]MK-801 binding without affecting the binding at equilibrium in a manner similar to that found with glycine, as well as with glutamate; Mg2+, however, facilitated the initial association rate with a concomitant reduction of the binding at equilibrium. Zn2+ was effective in accelerating the initial rapid phase of association, with the initial slow phase being delayed, and in markedly reducing the binding at equilibrium. Both Mg2+ and Ca2+ also facilitated dissociation of the bound [3H]MK-801 and Zn2+ slowed the dissociation in untreated membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Isolated prolonged retrograde amnesia.

We describe a patient who had isolated retrograde amnesia of 1-year duration without anterograde amnesia after recovery from encephalitis. Single photon emission computed tomography using 123I-IMP revealed that left temporal lobe abnormality. We postulate that the learning ability for new information and recalling ability for old information involve different neural structures, and there is a possible relationship between isolated retrograde amnesia and left temporal dysfunction.

Adult↗

PubMed1992

Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke.

To determine the effect of intravenous recombinant tissue plasminogen activator (rt-PA) on vascular and neurologic outcomes, we enrolled 31 patients with acute carotid artery-territory ischemic stroke within 6 hours from symptom onset in a randomized, double-blind, placebo-controlled study. We gave either rt-PA (duteplase at the dose of 20 or 30 mega-international units [MIU]) or placebo intravenously for 60 minutes in patients randomly assigned to the three groups. A comparison between the baseline and postinfusion angiograms showed that complete or partial reperfusion occurred in 50% (5/10) of patients treated with 30 MIU rt-PA, 44% (4/9) of those treated with 20 MIU rt-PA, and 17% (2/12) in the control group. In patients with middle cerebral artery occlusions, reperfusion occurred in 71% (5/7) of the 30-MIU group, in 67% (4/6) of the 20-MIU group, and in 13% (1/8) of the control group. Patients treated with 30 MIU rt-PA showed a significantly early and better clinical improvement, as measured by the neurologic scale, than did those treated with placebo. Parenchymal hemorrhage occurred in one patient in each group, and frequency of clinically insignificant hemorrhagic infarction was comparable among the treatment groups. No major systemic complications occurred in any group. These results support the efficacy of intravenous infusion of rt-PA soon after the onset of stroke in producing rapid thrombolysis and neurologic recovery; it may be of particular value in patients with thromboembolic occlusion in the middle cerebral artery.

Acute Disease↗

PubMed1992

Syntheses of recombinant yellowtail and flounder growth hormones in Escherichia coli.

For syntheses of recombinant yellowtail and flounder growth hormones (r-yGH and r-fGH) in E. coli, expression plasmids were constructed. The expression level of r-yGH and r-fGH in the host cells were very high, reaching 15 and 8% of the total protein, respectively. These product proteins were accumulated in inclusion bodies in the cells. The recombinant hormones were isolated from the pellets ina glutathione reduction/oxidation buffer. The refolded hormones were further purified by DEAE-Toyopearl 650M chromatography to homogeneity. The purified r-yGH and r-fGH were composed of 188 and 174 amino acid residues, respectively, having amino-terminal sequences starting with methionine. The recombinant hormones had potent growth-promoting activities on juvenile rainbow trout Salmo gairdneri in a dose-dependent manner.

Animals↗

PubMed1992

Prominent negative T waves with QT prolongation indicate reperfusion injury and myocardial stunning.

To observe the clinical course after reperfusion and recovery from myocardial stunning of the left ventricular anterior wall, we prospectively reviewed and analyzed cardiac enzymes, ECG changes, echocardiograms, and cineangiograms in 8 patients with the acute ischemic syndrome who fulfilled the following criteria: 1) no history of previous myocardial infarction, 2) repeated and/or prolonged episodes of chest pain, 3) critical stenosis of the left anterior descending artery with wall motion abnormalities, 4) successful emergency percutaneous transluminal coronary angioplasty, and 5) normal wall motion on repeat cineangiography 4 to 8 weeks later. Creatine kinase (CK) and/or its cardiac isoenzyme (CK-MB) were minimally elevated in all cases. Wall motion was normalized with the reduction of end-systolic volume (end-diastolic volume: from 139 +/- 25 to 140 +/- 37 ml, ns, end-systolic volume: from 68 +/- 16 to 39 +/- 13 ml, p < 0.001, ejection fraction: from 51 +/- 6 to 71 +/- 6%, p < 0.001). Serial echocardiograms showed normalization of wall motion within 4 to 28 days. T wave inversion in the left precordial leads developed 30 min to 5 hours after the cessation of chest pain or successful reperfusion, and prominent negative T waves (1.6 +/- 0.6 mV) with QT prolongation (0.56 +/- 0.08 sec) in V3 or V4 reached their peak values within one to 5 days. ECG abnormalities resolved after 21 to 95 days. These ECG findings may indicate reperfusion injury and the presence of myocardial stunning in the anterior wall of the left ventricle.

Aged↗

PubMed1992

[Adequate Ca level for dialysis patient (study on medical therapy for secondary hyperparathyroidism in dialysis patient)].

We evaluated our medical therapy of secondary hyperparathyroidism (2 degrees HPT) in dialysis patients. Ten hemodialysis patients with 2 degrees HPT (PTH-C; higher than 10ng/ml) were treated with vitamin D3, large amounts of phosphate binders and calcitonin and data over three years were examined. Our data showed that 2 degrees HPT is manageable by medical therapy. Furthermore, we suggest that the adequate Ca level for dialysis patients is to maintain the Ca (mEq/1) xP (mg/dl) at less than = 35. When plasma P is less than 6mg/dl. The maintenance of this Ca level successfully treated 2 degrees HPT, and this prevent the appearance of renal osteodystrophy (ROD) in dialysis patients.

Adult↗

PubMed1991

A broadly neutralizing monoclonal antibody that recognizes the V3 region of human immunodeficiency virus type 1 glycoprotein gp120.

Previous studies have demonstrated that the principal neutralizing determinant of human immunodeficiency virus type 1 (HIV-1) is located in the V3 loop of glycoprotein gp120. Antibodies prepared against this region using gp120 or peptides as immunogens have been predominantly HIV-1-isolate-specific. In the present studies, murine monoclonal antibodies (mAbs) were prepared against the HIV-1MN strain. One mAb, designated NM-01, was selected for its ability to neutralize both the MN and IIIB strains. Neutralization of H9-cell infectivity as determined by reverse transcriptase assay demonstrated an ID50 of less than 1 microgram/ml for both MN and IIIB. mAb NM-01 also blocked MN and IIIB infectivity in the MT-2 assay and inhibited their reactivity in syncytium formation. The results further demonstrate that mAb NM-01 binds to the V3 loop of gp120 at amino acids 312-326. This mAb reacted equally well with loop peptides from the MN, IIIB, RF, and CDC4 isolates. In contrast, there was less affinity with a similar peptide from the NY5 strain and little if any reactivity with loop peptides from the Z2, Z6, and ELI strains. We also demonstrate that peptides corresponding to the V3 loops of MN and IIIB, but not Z6, block neutralization of IIIB virus by mAb NM-01. These findings indicate that mAb NM-01 reacts with diverse HIV-1 isolates through the Gly-Pro-Gly-Arg sequence of the V3 loop.

Amino Acid Sequence↗

PubMed1991

Identification and characterization of specific binding sites of [3H]spermidine in synaptic membranes of rat brain.

Synaptic membranes of rat brain contained specific binding sites of [3H]spermidine (SPD) that exhibited an inverse temperature dependency, structure selectivity, reversibility, saturability, low affinity and high density with an uneven distribution profile. The affinities were not significantly different from each other in the rodent brain, while the highest density was found in the medulla-pons among the central structures examined with progressively lower densities in the midbrain, striatum, cerebellum, hypothalamus, hippocampus and cerebral cortex. The binding was insensitive to digestion by various proteases and glycosidases but sensitive to potentiation by phospholipases. A clear correlation was seen between the abilities of several natural and synthetic polyamines to displace [3H]SPD binding and to potentiate [3H] (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine binding to open cation channels associated with an N-methyl-D-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid receptors. Treatment of brain membranes with deoxycholic acid resulted in a significant solubilization of [3H]SPD binding sites. Furthermore, [3H]SPD markedly associated with the acidic phospholipid phosphatidylserine irrespective of the presence of synaptic membranes in a manner sensitive to inhibition by a variety of calmodulin antagonists. These results suggest that endogenous polyamines may play a stimulatory role in neuronal responses mediated by the NMDA receptor ionophore complex through an interaction between their positive charges and negative charges of membranous phosphatidylserine in rat brain.

Animals↗