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J Tatsuno

Publications and source records attributed to J Tatsuno.

At least 19 recordsLinked to original sources

Subtypes of adrenergic receptors and intracellular mechanisms involved in modulatory effects of noradrenaline on glutamate.

We have previously reported that the response of cultured chick cerebellar neurons to glutamate is enhanced by noradrenaline (NA) or isoproterenol and suppressed by clonidine. The present study was carried out to further specify the adrenergic receptor subtypes involved in the facilitatory effect of NA or isoproterenol and the suppressive effect of clonidine, and to examine the intracellular mechanisms underlying these modulatory effects of NA. The clonidine effect, which was mimicked by NA iontophoresed with large ejecting currents, was blocked by yohimbine and tolazoline (alpha 2 antagonists) and also by dibutyryl cyclic AMP or forskolin which augmented the glutamate response by itself. Prazosin, an alpha 1 receptor antagonist did not block the clonidine effect. NA- or isoproterenol-induced facilitation, which was mimicked by denopamine (beta 1 agonist), was antagonized by acebutolol (beta 1 antagonist) and not by ICI 118,551 (beta 2 antagonist). Pretreatment of neurons with pertussis toxin for more than 24 h blocked the suppressive action of clonidine without affecting the facilitatory action of isoproterenol. Furthermore, intracellular injection of GDP beta S inhibited the modulatory effects of either clonidine or isoproterenol. These results indicate that the facilitatory and inhibitory modulatory effects of NA may be mediated by beta 1 and alpha 2 receptors linked to cAMP systems, respectively, and the former is coupled with the stimulatory G protein (Gs) and the latter is with the inhibitory G protein (Gi).

Acebutolol

Time discrete model of recurrent inhibition in hippocampal dentate gyrus.

A time discrete model of recurrent inhibition in the hippocampal dentate gyrus is made and analyzed. This model assumes that (1) each granule cell can generate only one action potential in response to a single stimulation of the perforant path, (2) each interneuron receives synaptic inputs from many granule cells, and (3) an output of the interneuron is inhibitory for granule cells. Although each granule cell generates an action potential in the all-or-none fashion, the population spike is shown to be approximated by a piecewise linear function of the population excitatory post-synaptic potential (EPSP). From this model six patterns in the population spike responses to the paired-pulse stimulation are deduced. Each pattern is composed of some broken lines whose slopes and intercepts are explicitly expressed by the average and variance of the microscopic parameters and the population size of the cells. This model clarifies the relation between the measured quantity in the field potential experiment and the microscopic quantities peculiar to the granule cell and to the interneuron.

Action Potentials

The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes.

Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a lambda gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu160----His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a lambda max at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation (turnover number of 15 min-1) and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 kDa, the former of which appeared to correlate with human microsomal coumarin 7-hydroxylase activity. A more striking correlation was found between IIA mRNA and enzyme activity. The rat antibody was able to completely abolish coumarin 7-hydroxylase activity in 12 liver samples. In addition, kinetics of coumarin metabolism in two livers were monophasic over the substrate concentration tested. Km values obtained from human liver (2.3 microM) were similar to those obtained from lysates of hepatoma cells expressing IIA3 (3.6-7.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Dietary potassium influences kidney maintenance of serum phosphorus concentration.

In studying the metabolic effects of diet potassium (K+) variation in normal humans, we noted that varying diet K+ within its normal range influenced inorganic phosphorus (Pi) homeostasis and serum calcitriol (1,25-dihydroxyvitamin D) levels. In six men who ingested a constant whole-foods diet containing (per 70 kg body wt) 27 mmol/day Pi and 52 mEq/day K+, we increased diet K+ to 156 mmol/day with supplements first of potassium bicarbonate (KHCO3) alone and then of potassium chloride (KCL) alone, each for eight days interrupted by an eight-day recovery period of no K+ supplement. Urine Pi decreased promptly with either K(+)-salt, each inducing a persisting retention of 7 to 10 mmoles Pi, which was dumped during recovery. Fasting serum [Pi] increased with either K+ supplement (P = 0.022, repeated measures analysis of variance); the composite mean serum [Pi] for the two K(+)-supplement periods exceeded that for the two periods without supplements (P less than 0.01, paired t-test). Conversely, the concentrations of serum calcitriol decreased with either K+ supplement (P = 0.020). Among subjects, the diet K(+)-induced increases in serum [Pi] correlated with those in plasma [K+] (r = 0.64, P = 0.027); the decreases in serum calcitriol concentration correlated with the increases in serum [Pi] (r = -0.69, P = 0.014). There were no significant differences among periods in serum parathyroid hormone, ionized calcium, urine cyclic AMP excretion, plasma renin activity, body weight, serum albumin, or creatinine clearance; plasma volume decreased slightly during KCL but not during KHCO3 periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Normal diet NaCl variation can affect the renal set-point for plasma pH-(HCO3-) maintenance.

In humans who are ingesting abundant NaCl, blood pH (pHb) and plasma bicarbonate concentration [HCO3-)p) change little or imperceptibly in response to the ingestion of alkali salts. We tested the hypothesis that such tight homeostatic regulation is an artifact of eating a culturally imposed NaCl-enriched diet, not a fundamental physiological trait of humans. In five normal men ingesting a constant acid-producing diet with a low intrinsic NaCl content (0.15 mEq/kg of body weight per day), we measured plasma and urine acid-base composition during four 7-day periods in which the diet was supplemented as follows: no supplements----NaHCO3 only----NaHCO3 plus NaCl----NaCl only. Each sodium supplement was 2.0 mmol/kg body weight per day. With no supplements, pHb was 7.43 +/- 0.005 and (HCO3-)p was 25.0 +/- 0.4 mEq/L. When NaHCO3 only was added, pHb rose 0.02 (to 7.45 +/- 0.004; P less than 0.01) and (HCO3-)p rose nearly 4 mEq/L (to 28.9 +/- 0.6 mEq/L, P less than 0.001). The rise in (HCO3-)p was sustained predominantly by an increased rate of renal bicarbonate reabsorption. When NaCl was added, (HCO3-)p returned to the earlier level, despite continued NaHCO3 supplementation (24.9 +/- 0.6 mEq/L), and remained there when NaHCO3 supplementation was subsequently stopped (24.1 +/- 0.5 mEq/L). Thus, tight homeostatic regulation of plasma acid-base composition in response to a change in dietary base occurred only when dietary NaCl was abundant. To our knowledge, this is the first study in normal humans that demonstrates that diet NaCl variations within the normal range significantly influence plasma acid-base composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium

Effects of LTP-inducing tetanic stimulations of the perforant path on the commissural inhibition and facilitation of dentate granule cell discharge.

Effects of diazepam (1 mg/kg, i.p.) on the commissural influences on granule cells were first examined to further assess its GABAergic inhibitory mechanism. Whereas the commissural inhibition at an interval of 5-8 ms of the contralateral dentate-perforant path (CP) combined stimulus was not enhanced by diazepam, the commissural facilitation at a CP interval of 11-20 ms was reduced, suggesting that the GABAergic inhibition is involved in rather a part of the commissural facilitation at a CP interval of 11-20 msec than a part of the 'commissural' inhibition at a shorter CP interval. Based on the results of diazepam, effects of high-frequency stimulations of the perforant path on the commissural inhibition of dentate granule cells were then examined, in relation to their effects on the dentate paired-pulse depression. These stimulations produced the long-term potentiation of the perforant path-dentate excitatory synapse and significant reduction of the paired-pulse depression. The commissural inhibition at a CP interval of 5-8 ms remained unchanged following tetanization. The commissural facilitation at a CP interval of 11-20 ms was, however, slightly enhanced by tetanic stimulations and a statistical significance was obtained at a CP interval of 19 ms. These results imply that tetanic stimulations of the perforant path selectively reduce the GABAergic component of the commissural inhibition, as well as that of the paired-pulse depression.

Action Potentials

Long-lasting reduction of dentate paired-pulse depression following LTP-inducing tetanic stimulations of perforant path.

Effects of high-frequency stimulations of the perforant path on the dentate paired-pulse depression were examined in urethane-anesthetized rats. The tetanic stimulations produced a long-term potentiation (LTP) of the excitatory synaptic transmission at the perforant path-dentate granule cell synapses in almost all animals examined. The strength of the early paired-pulse depression at an inter-pulse interval (IPI) of 20 ms decreased significantly for at least 60 min after the tetanic stimulations, whereas the late paired-pulse depression at an IPI of 2 s remained almost unchanged. The reduction of the early paired-pulse depression was stepwise augmented by each of successive tetanic stimulations given at an interval of 10 min. A preceding antidromic stimulation of the mossy fibers depressed the population spike amplitude of perforant path response at an interval of 5-9 ms. The strength of the antidromic depression of population spike also decreased following the perforant path tetanic stimulations. These results suggest that tetanic stimulations of the perforant path produce a long-lasting reduction of the GABAergic recurrent inhibition in the dentate area associated with LTP. The possible mechanisms of the decrease in GABAergic inhibition produced by tetanic stimulations and its possible effects on the development of LTP with succeeding tetanic stimulations were discussed.

Action Potentials

Microcomputer-controlled laboratory system for field potential experiments.

A microcomputer-controlled laboratory system for hippocampal field potential experiments was constituted. This system realized the quasi-simultaneous processing of execution of stimulation, data acquisition, data display and data analysis by means of a microcomputer for the first time. To attain this quasi-simultaneous processing, a new algorithm for drawing a tangent on the wave-form of the potential was contrived, which enabled rapid analysis of an arbitrary population spike even in the case of generation of double spikes. The system has the following functions: (1) execution of the programmed stimulation paradigm, (2) analog/digital (A/D) conversion of the evoked field potential with a sampling interval of more than 50 microseconds per channel, (3) display of the A/D converted wave-form data on a CRT and storage of the data on a floppy disk, (4) on-line analysis of the population excitatory postsynaptic potential (EPSP) and population spike, (5) more detailed off-line analysis of the field potentials, and (6) output of the wave-form data and measured values through a printer and an X-Y plotter.

Action Potentials

Characterization of excitatory amino acid receptors in cultured chick cerebellar neurons.

In order to characterize excitatory amino acid receptors in cultured chick cerebellar neurons, the effects of amino acid agonists on the input resistance and the antagonist specificity of the depolarization induced by each agonist were intracellularly studied. In Mg-containing medium, glutamate (especially at low doses), aspartate and N-methyl-D-aspartate not only decreased the input resistance at depolarized membrane potentials but also increased it at around the resting potential. In Mg-free medium, glutamate (high and low doses) and all other agonists simply decreased the input resistance. The effects of antagonists on amino acid-induced depolarizations in Mg-free medium were as follows: Mg and alpha-aminoadipate blocked N-methyl-D-aspartate and aspartate most strongly, glutamate and kainate moderately, and quisqualate only slightly; 2-amino-4-phosphonobutyrate antagonized N-methyl-D-aspartate most strongly, aspartate moderately and others mildly; 2-amino-5-phosphonovalerate blocked aspartate most strongly and others mildly; gamma-D-glutamylglycine blocked kainate most strongly and others moderately; and kynurenate was rather nonselective but most strongly antagonized N-methyl-D-aspartate and aspartate. These results suggest that all receptor subtypes (N-methyl-D-aspartate-, quisqualate- and kainate-types) are present in cultured chick cerebellar neurons, but their antagonist specificities are different from those in other central neurons, and also that glutamate at a low dose activates N-methyl-D-aspartate receptors, while it acts on quisqualate receptors at a high dose.

Amino Acids

Continuous changes in electroencephalographic topograms and auditory reaction time during simulated 21 ATA (atmospheres absolute) heliox saturation dives.

The present study was designed to investigate EEG changes during two simulated 21 ATA hyperbaric heliox saturation dives. Four professional male divers were attached to 13 electrodes over the scalp and compressed to 21 ATA by helium. Throughout the dives, EEGs were measured and stored on a magnetic FM tape recorder to calculate electroencephalographic topograms. Three patterns of slow wave increase were clearly distinguished by the electroencephalographic topogram during compression. The first pattern was caused by trains or bursts of theta waves which spread from the frontal region to the central region of the scalp. This pattern occurred at comparatively shallow depth and showed the slowest recovery during the bottom stage among three patterns. The second pattern found in two divers was caused by frontal midline theta bursts, which showed maximum activity at F2. The frontal midline theta bursts were augmented by a reaction time task. The third pattern was caused by vertex sharp waves which indicated a transition from sleep stage 1 to sleep stage 2. Neurophysiological meanings of these EEG patterns as well as the relationship between EEG changes and other indices were discussed.

Adult

Effects of noradrenaline on the responsiveness of cultured cerebellar neurons to excitatory amino acids.

The effects of noradrenaline (NA) on the responsiveness of cultured cerebellar neurons to excitatory amino acids were intracellularly investigated. NA applied to external medium to a final concentration of 10 microM or lower slightly decreased the firing frequency of spontaneous spikes, induced a small hyperpolarization or slightly increased the input resistance of Purkinje cells. In addition, bath-applied NA was found to enhance the depolarizations induced by iontophoretically applied glutamate and aspartate but to a smaller extent for the latter. These direct and modulating effects of NA were also observed when NA was applied by iontophoresis. The sites sensitive to iontophoresed NA were found to be not uniformly distributed but localized in restricted regions on individual Purkinje cells. The enhancement by NA of the glutamate or aspartate response was blocked by beta-adrenergic antagonists, propranolol or pindolol, and extracellularly applied cAMP mimicked the NA action. These results suggest the possibility that NA physiologically modulates excitatory amino acid-mediating synaptic transmission in the cerebellum probably by acting on beta-rather than alpha-adrenergic receptors.

Action Potentials

Objective evaluation of differences in patterns of EEG topographical maps by Mahalanobis distance.

The purpose of this work was to develop a method to objectively evaluate differences in topographical patterns between 2 groups of isopotential maps. Previous evaluations by other investigators had been based on subjective judgment which created problems in describing differences in patterns, particularly when the differences were subtle. In the method presented in this report, the differences are evaluated by the Mahalanobis distance calculated from polynomial coefficient vectors obtained from unbiased polynomial interpolation in order to calculate values of picture elements in the 2-dimensional maps. One polynomial coefficient vector corresponds to one pattern of the map, containing both EEG and locational information. Examples of the evaluation are shown in the maps of fast activities induced by the injection of thiopental, diazepam or both drugs to an adult volunteer. In 5 experimental situations (A, control; B, thiopental; C, thiopental and diazepam; D, diazepam; and E, diazepam and thiopental administration), the polynomial coefficient vectors were obtained. When Mahalanobis distances (Q value) between the 2 maps for the 5 situations, arranged in 8 different combinations, were calculated, the values corresponded significantly to the pattern differences found between the maps. The greater the Q value, the more dominant the pattern difference. The objective evaluation method presented in this report has significant advantages over the subjective method previously reported and should be of interest to investigators attempting to quantify topographical pattern differences.

Adult

Age associated alteration of lidocaine metabolism is position selective.

Patterns of associated alterations in N-deethylation, 3-hydroxylation, and aromatic methylhydroxylation of a single substrate, lidocaine in liver microsomes from 0.7 - 28 months old Fischer 344 rats were examined. These three patterns were all different from one another. In addition to this position selectiveness, a clear sex difference was observed in the pattern of alteration in N-deethylation. These results are consistent with the hypothesis that age associated alterations in drug metabolism are caused by age associated alterations in relative abundance of multiple species of cytochrome P-450.

Aging

Development of sensitivity to GABA and glycine in cultured cerebellar neurons.

The effects of iontophoretically applied gamma-aminobutyric acid (GABA) and glycine on developing cerebellar neurons cultured for 7-40 days were intracellularly investigated. All neurons tested dose-dependently responded to both GABA and glycine. In mature neurons (after 25 days in culture) these amino acids inhibited spontaneous spikes, decreased the membrane input resistance and induced either hyperpolarization or depolarization of membrane potential. The mean reversal potential was -47 mV for GABA and -43 mV for glycine. Immature neurons, 7-12 days in culture, which were not spontaneously firing, also behaved in a similar manner as the mature ones, though the membrane resistance was not so largely changed by GABA or glycine and the reversal potential was more positive (-39 mV for GABA, -37 mV for glycine). These reversal potentials were shifted toward 0 mV by lowering the external Cl- concentration in either mature or immature neurons. The effects of GABA and glycine on mature or immature neurons were more or less inhibited by all of picrotoxin, bicuculline and strychnine. The effective concentrations of these antagonists, however, were lower in general in immature neurons. In mature neurons, picrotoxin and bicuculline became more selective to GABA than glycine and strychnine became more selective to glycine than GABA. These results suggest that sensitivities to GABA and glycine differentiate into selective types in the course of maturing of cerebellar cultured neurons.

Action Potentials