Biomedical subjects

E Tanaka

Publications and source records attributed to E Tanaka.

At least 379 records · Page 21Linked to original sources

PubMed1993

Clinical significance of antibodies to nonstructural and core proteins of hepatitis C virus in posttransfusion hepatitis patients during long-term follow-up.

To clarify the long-term clinical significance, antibody to hepatitis C virus (HCV) was examined using core (p22) and nonstructural (C100-3) protein assays in sera of 18 patients with non-A,non-B posttransfusion hepatitis (PTH-NANB) who were selected retrospectively. Each patient had been followed for more than 5 years after the development of the disease. They were divided into three groups according to clinical outcome: acute hepatitis that resolved within 1 year, group 1 (n = 3); chronic hepatitis that resolved within 1-4 years, group 2 (n = 4); and chronic hepatitis that persisted for 5 years or longer, group 3 (n = 11). Sixteen of the 18 were positive for anti-C100-3 and anti-p22, one was positive for anti-p22 alone, and one was negative for both. In ten of the 16 (62.5%), anti-p22 appeared before anti-C100-3. The anti-C100-3 titer peaked about 12 months after disease onset in all cases and thereafter declined gradually, finally becoming negative in groups 1 and 2, while the titer fluctuated in group 3. The mean titer in group 3 at 12 months (69.2 units) significantly exceeded that of groups 1 (4 units) and 2 (8.2 units). Group 1 was seronegative for HCV antibodies and HCV RNA at the last examination, suggesting the cessation of HCV replication. Group 3 remained positive for those markers, indicating the continued replication of HCV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Tension and intracellular calcium transients of activated ferret ventricular muscle in response to step length changes.

To elucidate the effects of mechanical constraints on the (Ca2+) affinity of cardiac troponin C, we studied the relationships among the myoplasmic Ca2+ concentration ([Ca2+]i), tension and length in steadily activated intact cardiac muscle. The Ca2+ sensitive photoprotein, aequorin, was micro-injected into cells of ferret right ventricular papillary muscles to monitor the [Ca2+]i. The muscle was then steadily activated with ouabain (10(-4) M)(ouabain contracture) or high frequency stimuli in the presence of ryanodine (5 microM)(tetanic contraction); the tension and aequorin light (AL) transients in response to a step length change were then analyzed. The tension transient response to either the stretch or release in length was oscillatory: tension decreased rapidly during the release and then increased, after which it lapsed into a new steady level in a series of damped oscillations. The opposite was true for the stretch. The oscillatory responses were conspicuous and less damped in the ouabain contracture. The transient AL response was also oscillatory, the time course of which corresponded exactly to that of the tension transient response, though no detectable changes in AL were observed at the initial phase of the stretch response. The increase in AL corresponded exactly to the decrease in tension, likewise the decrease in AL to the increase in tension. The steady level of AL after release was decreased in ouabain contracture, but was increased in tetanic contraction. These results suggest that the Ca2+ affinity of cardiac troponin C is increased with an increase in tension (i.e., the cross-bridge attachment) and decreased with a decrease in tension (i.e., the cross-bridge detachment), and that the myoplasmic calcium concentration is lowered by release, at least in a Ca(2+)-overloaded condition, mainly through the sarcoplasmic reticulum.

Aequorin↗

PubMed1993

N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung.

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (Kd) values of 53 +/- 2 and 4687 +/- 124 nM and maximum binding capacity (Bmax) values of 7 +/- 1 and 133 +/- 27 pmol/mg protein (n = 5) respectively. The IC50 values of various amines were as follows: IMP, 9 x 10(-5) M; propranolol, 5 x 10(-4) M; haloperidol, 6 x 10(-4) M; ketamine, 9 x 10(-3) M; dopamine, 1 x 10(-2) M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with Kd values of 54 +/- 2 and 5277 +/- 652 nM and Bmax values of 7 +/- 1 and 103 +/- 21 pmol/mg protein (n = 3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue.

Adult↗

PubMed1993

Comparison of the clinical and immunogenetic features between patients with autoimmune hepatitis and patients with type C chronic active hepatitis.

We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis (C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C-CAH, they were rare in patients with AI-CAH. The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH predominantly. Ongoing or past infection of HCV was seen in only 14% of patients with AI-CAH. HLA-DR4 was the most frequently associated with AI-CAH (89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted, disease, and different from C-CAH which is a viral infectious disease.

Adult↗

PubMed1993

Comparison of seroepidemiology of hepatitis C in blood donors between Bangladesh and Japan.

To compare the seroepidemiology of hepatitis C and hepatitis B between Bangladesh and Japan, we tested the second generation antibody to hepatitis C virus (anti-HCV-2) and hepatitis B surface antigen (HBsAg) in serum samples from 163 professional blood donors (161 males and 2 females, mean age 28.6 yr.) and 83 voluntary blood donors from Bangladesh, and 7479 Japanese voluntary blood donors (5036 males and 2443 females; mean age 37.1 yr.). In Bangladesh, anti-HCV-2 is detected in 2.4% of professional blood donors and 0% of voluntary blood donors, furthermore, HBsAg is detected in 29% and in 2.4% of professional and voluntary blood donors, respectively. In Japan, anti-HCV-2 is detected in 0.6% in voluntary blood donors, and HBsAg also in 0.6%. These results indicate that professional blood donors in Bangladesh are highly contaminated by hepatitis B virus and moderately by hepatitis C virus, while voluntary blood donors in both countries are not so highly contaminated by either hepatitis viruses.

Adult↗

PubMed1993

Evidence for 5-HT2 receptor involvement in the stimulation of preovulatory LH and prolactin release and ovulation in normal cycling rats.

The participation of serotonin (5-HT) in the control of LH secretion and ovulation has been reported in numerous pharmacological experiments, although the results have been contradictory. In this study to determine the physiological involvement of 5-HT2 receptors in the control of preovulatory LH and prolactin (PRL) release and ovulation, ketanserin (KET), a selective 5-HT2 receptor antagonist, was administered to normal cycling rats. Oral administration of KET at 10 mg/kg BW between 0900h and 1300h on the day of proestrus completely blocked ovulation, while the administration after 1500h did not. The ovulation was confirmed 2 days after treatment with KET. There was no consistent effect on the number of ova ovulated. Co-administration of KET with 5-methoxy-N,N-dimethyltryptamine (5-MeDMT), a 5-HT agonist, at a dose of 2 mg/kg BW ip reversed KET-induced inhibition of ovulation. The highest rate (89%) of reversal was obtained by co-administration at 1500h. KET administered at 1100h completely blocked the preovulatory surge of LH and PRL observed in control animals at 1800h. The present study suggests that 5-HT stimulates preovulatory LH and PRL surge and ovulation via 5-HT2 receptor under physiological conditions and that the effect of 5-HT depends on the critical period and the 24-hour periodicity.

Animals↗

PubMed1993

Serotonin stimulates steroidogenesis in rat preovulatory follicles: involvement of 5-HT2 receptor.

The role of serotonin (5-HT) in the regulation of steroidogenesis in the ovary via 5-HT2 receptor was studied in normal cycling rats and their preovulatory follicles. Oral administration of ketanserin (KET), a selective 5-HT2 antagonist, at 10 mg/kg BW at 1100h on the day of proestrus resulted in a marked decrease in serum estradiol levels immediately after the administration. 5-HT stimulated estradiol secretion by preovulatory follicles incubated for 5 hrs in Krebs-Ringer bicarbonate buffer. 5-HT (2.5 microM) -enhanced estradiol secretion was inhibited by KET (1-100 microM) in a dose-dependent manner. Secretion of progesterone and testosterone was also inhibited by about the same order of magnitude as estradiol. Addition of pregnenolone (1 microgram/ml) prevented the KET-inhibited progesterone production. Both testosterone and estradiol increased at the same ratio by the addition of progesterone (1 microgram/ml). The inhibition of secretion of these hormones was overcome by dbcAMP (0.1 mM). The present study suggests that 5-HT stimulates steroidogenesis in the metabolic pathway prior to pregnenolone in rat preovulatory follicles and the action of 5-HT could possibly be mediated by a 5-HT2 receptor.

Animals↗

PubMed1993

Proliferative activity of hepatocytes in chronic viral hepatitis as revealed by immunohistochemistry for proliferating cell nuclear antigen.

Liver biopsy specimens of 65 cases of chronic viral hepatitis, including 29 cases of type B, 34 cases of type C, and two cases of non-A, non-B, non-C type, were immunohistochemically stained for proliferating cell nuclear antigen (PCNA) to evaluate the proliferative activity of hepatocytes. According to a histopathologic evaluation using the histology activity index (HAI) scoring system, chronic persistent hepatitis and chronic active hepatitis were clearly differentiated with no overlapping of the score. The labeling indices of PCNA of hepatocytes in chronic persistent hepatitis had a significant relationship with HAI scores (r = .54), suggestive of a contribution of lobular hepatocyte necrosis and/or portal inflammation to the regenerative rate of hepatocytes, but did not exceed 3.0%. On the other hand, 11 of 47 cases of chronic active hepatitis showed PCNA labeling indices higher than 3.5% without any significant relationship with the HAI scores. There was no significant difference, however, of distribution of HAI scores or PCNA labeling indices between hepatitis types B and C. Based on current concepts of the role of hepatocyte proliferation in the development of liver cirrhosis and hepatocellular carcinoma, the present results suggest that the high proliferative rate of hepatocytes subject to the persistent liver cell injury in chronic active hepatitis may be related to a reconstruction pattern of the liver in cases of progression to cirrhosis and development of hepatocellular carcinoma.

Biomarkers, Tumor↗

PubMed1993

Ionic mechanisms underlying the depolarizing and hyperpolarizing afterpotentials of single spike in guinea-pig cingulate cortical neurons.

Intracellular recordings and hybrid single-microelectrode voltage-clamp techniques were used to study the ionic mechanisms underlying the afterdepolarization and the subsequent slow afterhyperpolarization that followed a single action potential in layers V/VI neurons of the guinea-pig anterior cingulate cortex in in vitro slices. Both the afterdepolarization and afterhyperpolarization were markedly suppressed in size by addition of Co2+ or Cd2+, reduction in extracellular Ca2+, and intracellular EGTA injection. On the other hand, elevation of extracellular Ca2+ concentration augmented the amplitudes of the afterpotentials. The afterdepolarization amplitude was selectively depressed by the stilbene derivatives, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonate, disodium 3H2O, and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid, disodium salt. Reduction in external Cl- and intracellular Cl- injection enhanced the afterdepolarization amplitude without affecting the afterhyperpolarization. The null potentials for the afterdepolarizations recorded with K acetate- and Cs acetate-electrodes were -68 and -63 mV, respectively. The slope of the null potential obtained with K acetate electrodes or Cs acetate electrodes was 49 and 53 mV, respectively, per log unit of the external Cl- concentration. Reduction in external K+ markedly depressed the afterdepolarization and augmented the afterhyperpolarization in size, whereas rise in external K+ markedly augmented the afterdepolarization and depressed the afterhyperpolarization. The null potential for the afterhyperpolarization recorded with K acetate electrodes was -94 mV. The slope of the null potential was 57 mV per log unit of the external K+ concentration. Reduction in extracellular Na+ concentration slightly depressed both the amplitudes of the afterdepolarization and afterhyperpolarization. A hybrid voltage-clamp analysis revealed a slow decaying inward current and a subsequent outward current that followed an action potential. Both the amplitudes of the inward current corresponding to afterdepolarization and the outward current corresponding to afterhyperpolarization were suppressed by addition of Co2+. Reduction in extracellular Cl- concentration augmented the inward current amplitude without significantly affecting the outward current. These results indicate that the afterdepolarization is mainly due to an increase in a Ca(2+)-activated Cl- conductance, while the afterhyperpolarization is mainly generated by an activation of Ca(2+)-mediated K+ conductance.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1993

Trimethadione metabolism as a probe drug to estimate hepatic oxidizing capacity in rats.

1. Trimethadione (TMO) has the properties required of probe drugs for the evaluation of hepatic oxidizing capacity in vivo. 2. TMO is demethylated to dimethadione (DMO), its only metabolite, in the liver after oral administration. 3. In rats with various types of hepatic intoxicated-, induced- and partially hepatectomized-rats, the serum DMO/TMO ratios, which were measured on blood samples obtained by a single collection 2 hr after oral administration of TMO, correlated well with the degree of hepatic damage or induction. 4. This finding suggests that TMO may be used as a probe drug in the rapid determination of the functional reserve mass of the liver as well as the hepatic oxidizing capacity.

Animals↗

PubMed1993

Microtubule-dependent control of cell shape and pseudopodial activity is inhibited by the antibody to kinesin motor domain.

One of the major functions of cytoplasmic microtubules is their involvement in maintenance of asymmetric cell shape. Microtubules were considered to perform this function working as rigid structural elements. At the same time, microtubules play a critical role in intracellular organelle transport, and this fact raises the possibility that the involvement of microtubules in maintenance of cell shape may be mediated by directed transport of certain cellular components to a limited area of the cell surface (e.g., to the leading edge) rather than by their functioning as a mechanical support. To test this hypothesis we microinjected cultured human fibroblasts with the antibody (called HD antibody) raised against kinesin motor domain highly conserved among the different members of kinesin superfamily. As was shown before this antibody inhibits kinesin-dependent microtubule gliding in vitro and interferes with a number of microtubule-dependent transport processes in living cells. Preimmune IgG fraction was used for control experiments. Injections of fibroblasts with HD antibody but not with preimmune IgG significantly reduced their asymmetry, resulting in loss of long processes and elongated cell shape. In addition, antibody injection suppressed pseudopodial activity at the leading edge of fibroblasts moving into an experimentally made wound. Analysis of membrane organelle distribution showed that kinesin antibody induced clustering of mitochondria in perinuclear region and their withdrawal from peripheral parts of the cytoplasm. HD antibody does not affect either density or distribution of cytoplasmic microtubules. The results of our experiments show that many changes of phenotype induced in cells by microtubule-depolymerizing agents can be mimicked by the inhibition of motor proteins, and therefore microtubule functions in maintaining of the cell shape and polarity are mediated by motor proteins rather than by being provided by rigidity of tubulin polymer itself.

Animals↗

PubMed1993

Biomechanical changes of the mandible from orthopaedic chin cup force studied in a three-dimensional finite element model.

Biomechanical changes of the mandible from orthopaedic chin cup forces were investigated by means of finite element analysis. A three-dimensional model of the mandible including the temporomandibular joint was developed for stress analysis in the mandible. A chin cup force of 400 gf was applied at pogonion on the mandible in the direction toward the condyle. From the stress analyses, it was revealed that (1) uniform tensile stresses were produced at the outer borders of the mandible, (2) compressive stresses were induced in the centre of the mandible, (3) compressive stresses were generated widely on the surface of the condyle, and (4) stresses on the condyle were smaller in magnitude than those in the mandibular corpus. These results coincide with morphological changes of the mandible revealed in previous studies and, thus, indicate an association of stresses with remodelling of the mandible from chin cup therapy applied to adolescent patients with mandibular prognathism.

Adolescent↗

PubMed1993

Comparison of hepatic drug-oxidizing activity after simultaneous administration of two probe drugs, caffeine and trimethadione, to human subjects.

Pharmacokinetic interactions between caffeine 2 mg/kg and trimethadione 4 mg/kg were evaluated in 10 healthy volunteers. Whether administered alone or together, the total body clearance (CL), the apparent volume of distribution (Vd) and half-life (t1/2) of caffeine and trimethadione were the same, however, there was a weak correlation between the CL of caffeine and trimethadione [alone: r = 0.51 (P < 0.05); coadministered: r = 0.56 (P < 0.05)]. There were also weak correlations between the CL of trimethadione and the area under the serum concentration-time curves (AUC) of theobromine (r = -0.61, P < 0.05), paraxanthine (r = -0.69, P < 0.05) and theophylline (r = -0.60, P < 0.05), when the two drugs were administered alone. After combined administration, the correlation between the CL of trimethadione and the AUCs of the metabolites of caffeine were as follows: theobromine r = -0.63 (P < 0.05); paraxanthine r = -0.68 (P < 0.05); theophylline r = -0.65 (P < 0.05). These findings suggest that caffeine and trimethadione metabolism in healthy subjects is mediated by only in part by a form(s) of P450 enzymes involved.

Adult↗

PubMed1993

Membrane properties and synaptic potentials of three types of neurone in rat lateral amygdala.

1. Intracellular recordings were made from the lateral nucleus of the amygdala in tissue slices cut from rat brain and maintained in vitro. 2. Three types of neurones were distinguished according to the after-potential that followed an action potential. Type 1 cells (44%, n = 225) had depolarizing after-potentials, resulting from a calcium-dependent chloride conductance. Type 2 cells (48%) had long-lasting (> 250 ms) hyperpolarizing after-potentials and type 3 cells (8%) had shorter hyperpolarizing after-potentials. The average resting potentials of the three cell types were -78, -69 and -62 mV respectively. Intracellular labelling with biocytin showed that type 1 cells were pyramidal neurones; type 2 and type 3 cells were non-pyramidal. 3. Experiments with receptor antagonists identified synaptic potentials mediated by excitatory amino acids and by GABA (acting at GABAA receptors) in all three cell types. A longer duration inhibitory synaptic potential resulting from activation of GABAB receptors was present in type 1 (pyramidal) and type 2 cells. 4. Cholecystokinin (100 nM to 1 microM) depolarized type 2 and type 3 cells but had no effect on type 1 (pyramidal) cells. Baclofen (1-3 microM) hyperpolarized type 1 and type 2, but not type 3 cells. [Met5]enkephalin (1-10 microM) hyperpolarized only type 2 cells. 5. It is concluded that the lateral nucleus of the amygdala contains pyramidal neurones and two types of non-pyramidal neurone; these can be differentiated by membrane properties, synaptic inputs and sensitivities to transmitters.

Action Potentials↗

PubMed1993

Alterations in contractile properties and Ca2+ transients by beta-and muscarinic receptor stimulation in ferret myocardium.

1. To clarify the mechanism which regulates the time course of twitch tension when beta- and muscarinic receptors are stimulated, intracellular Ca2+ transients, Ca2+ sensitivity of the contractile element and the cross-bridge cycling rate (CCR) were measured in ferret ventricular muscles. 2. Isoprenaline (Iso; 0.1 microM) increased peaks of Ca2+ transients measured with aequorin and tension, and abbreviated the time courses of both signals. Addition of acetylcholine (ACh; 0.01-1 microM) to the Iso-treated preparation dose dependently decreased the peaks of both signals and restored the time course of Ca2+ transients. However, the time course of tension was not recovered by the addition of ACh, and the relaxation time in particular, was further shortened by ACh. Carbachol (1 microM) applied to the Iso-treated preparation yielded similar results. 3. [Ca2+]i and tension at a quasi-steady level of tetanic contraction, which was produced by ryanodine (5 microM) and repetitive stimulation, were measured and Ca2+ sensitivity of the contractile element was estimated. Iso (0.1 microM) decreased the Ca2+ sensitivity and the addition of ACh (1 microM) completely recovered it to the control level. 4. In order to measure CCR, the perturbation analysis method was applied to steady-state tension of tetanic contraction. The CCR was not altered even when the tetanic tension level was decreased to 50% by decreasing [Ca2+]o. Iso (0.1 microM) slightly decreased the tetanic tension level and increased the CCR from 2.73 to 3.25 Hz. The effect of Iso was observed when the Iso-decreased tension was recovered by an increase in [Ca2+]i. The addition of ACh (1 microM) recovered the CCR which was increased by Iso, to the control level. Atropine (10 microM) blocked the effect of ACh, and carbachol (1 microM) restored the CCR increased by Iso to the control level. 5. The time course of Ca2+ transients, Ca2+ sensitivity and CCR were antagonistically regulated by beta- and muscarinic receptor stimulation, but the time course of tension did not parallel the changes in these parameters. Therefore, these results suggest that the time course of tension, particularly the relaxation time, is not determined by the time course of Ca2+ transients, Ca2+ sensitivity and the CCR, and that other factors might be involved in the regulation of the time course of tension when beta- and muscarinic receptors are stimulated.

Acetylcholine↗

PubMed1993

Mechanism of the effects of acetylcholine on the contractile properties and Ca2+ transients in ferret ventricular muscles.

1. We investigated the mechanism of signal transduction during the effect of muscarinic receptor stimulation on Ca2+ transients, tension, Ca2+ sensitivity and the cross-bridge cycling rate (CCR). 2. Membrane-permeable derivatives of cyclic GMP (8-bromo-cyclic GMP and dibutyryl cyclic GMP) did not cause any significant changes in the peaks of Ca2+ transients and tension and the time courses of either signal modulated by isoprenaline (Iso) (0.1 microM). 3. Nitroprusside (0.1-1 mM) likewise did not change the peaks or the time courses of Ca2+ transients and tension in the Iso-treated preparations. 4. In papillary muscles excised from ferrets treated with pertussis toxin (islet-activating protein, IAP), which is known to abolish the function of GTP-binding proteins (Gi, Go and Gt), similar changes in Ca2+ transients and tension produced by treatment with Iso (0.1 microM) were noted as in non-IAP-treated preparations. However, no effects of acetylcholine (ACh; 1 microM) on either signal were observed. 5. The relation between [Ca2+]i and tension measured during the steady state of tetanic contraction was shifted to the right by Iso (0.1 microM), and cyclic GMP derivatives (1 mM) did not change the altered relation. In the IAP-treated preparations, ACh (1 microM) did not influence the relation altered by Iso (0.1 microM). 6. Cyclic GMP derivatives (1 mM) did not alter the Iso (0.1 microM)-increased CCR measured by perturbation analysis. ACh (1 microM) did not restore the Iso-increased CCR in the IAP-treated preparations. 7. These results suggest that signal transduction in muscarinic receptor stimulation is primarily mediated by inhibition of adenylate cyclase via IAP-sensitive GTP-binding proteins, and that cyclic GMP does not play an important role in the effect of muscarinic receptor stimulation on Ca2+ transients, tension, Ca2+ sensitivity or CCR.

Acetylcholine↗

PubMed1993

Alterations in intracellular calcium and tension of activated ferret papillary muscle in response to step length changes.

1. To study the effects of mechanical constraints on the calcium (Ca2+) affinity of cardiac troponin C, we analysed the tension and aequorin light (AL, intracellular Ca2+) transients in response to a step length change in aequorin-injected ferret right ventricular papillary muscles. The muscle preparations were continuously activated with ouabain (10(-4) M) (ouabain contracture) or with high frequency stimuli in the presence of ryanodine (5 microM) (tetanic contraction). 2. The tension transient in response to either the release or stretch was oscillatory: tension decreased rapidly during the release and then increased, after which it lapsed into a new steady level in a series of damped oscillations. The opposite was true for the stretch. The oscillatory responses were conspicuous and less damped in ouabain-activated preparations (oscillation frequency of 2.2-2.3 Hz at 22 degrees and 4.5-4.6 Hz at 30 degrees C) and much more damped in ryanodine-treated preparations. 3. The transient AL response was also oscillatory, the time course of which corresponded to that of the transient tension response. Regardless of the difference in the time course of the transients in two different preparations and at two different temperatures, the increase in AL corresponded to the decrease in tension, likewise the decrease in AL to the increase in tension. 4. The mean level of AL after release was lower than the control level present just prior to the release in ouabain-activated preparations, but the AL after release finally returned to the nearly control level in ryanodine-treated preparations. 5. When the ryanodine-treated muscle was further treated with 2,3-butanedione monoxime (BDM) (20 mM), the tetanic tension decreased remarkably without affecting the AL signal. The tension transient of this preparation was quite similar to that of the resting muscle, which changed in a nearly stepwise fashion; AL was hardly affected by step length changes, as in the resting muscle, in spite of the higher AL level. 6. These results suggest that the Ca2+ affinity of cardiac troponin C is increased with an increase in tension (i.e. the cross-bridge attachment) and decreased with a decrease in tension i.e. the cross-bridge detachment), and that the mean [Ca2+]i is lowered by release, at least in a Ca(2+)-overloaded condition, mainly through the sarcoplasmic reticulum.

Aequorin↗

PubMed1993

Actions of 5-hydroxytryptamine on neurons of the rat cingulate cortex.

1. Intracellular recordings were made from layer V pyramidal neurons in slices of rat cingulate cortex. Electrodes contained potassium methylsulphate and biocytin for subsequent histology. 2. Synaptic potentials were separated pharmacologically with DL-2-amino-5-phosphonovaleric acid (APV), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), bicuculline, and 2-hydroxysaclofen into components mediated, respectively, by N-methyl-D-aspartate (NMDA) type excitatory amino acid, non-NMDA type excitatory amino acid, gamma-aminobutyric acid (GABAA), and GABAB receptors. Components mediated at excitatory amino acid, GABAA and GABAB receptors reversed polarity at -11, -76, and -108 mV, respectively. 3. When synaptic potentials were evoked by stimulation to the subcortical white matter, 5-hydroxytryptamine (5-HT; 1-100 microM) reversibly reduced the amplitude of NMDA, non-NMDA, GABAA, and GABAB components. Selective agonists and antagonists were used to show that this resulted from activation of 5-HT1B receptors. 4. When synaptic potentials were evoked by stimulation within layer V, 5-HT reduced the amplitude only of the NMDA and non-NMDA components but did not affect the GABAA and GABAB components. 5-HT did not change the amplitude of depolarizations evoked by direct application of glutamate. 5. It is concluded that 5-HT presynaptically inhibits the release of excitatory amino acids at synapses onto prefrontal pyramidal neurons and at synapses onto local feed-forward inhibitory interneurons. 6. 5-HT also hyperpolarized, depolarized, or did not change the membrane potential. The hyperpolarization involved 5-HT1A receptors and resulted from potassium conductance increase. The depolarization involved 5-HT2 receptors and resulted from potassium conductance decrease.

Animals↗