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1.
2.
Bi-Hua BIE Yong CHEN Zhi-Qi ZHAO Institute of Neurobiology Fu-Dan University Shanghai China Institute of Shanghai Physiology Chinese Academy of Sciences Shanghai China 《中国神经科学杂志》2006,(2)
Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinoci-ceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency ( PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat. 相似文献
3.
AClinicalStudyofReversingLeftVentricularHypertrophyinHypertensivePatientsbyAdalatZhangFumin(张馥敏)XuDi(许迪)YongYonghong(雍永宏)Chen... 相似文献
4.
Prediction of steady state bioequivalence relationships using single dose data II-nonlinear kinetics
A J Jackson 《Biopharmaceutics & drug disposition》1989,10(5):489-503
Two nonlinear pharmacokinetic models were simulated to investigate the relationship between single and multiple dose bioequivalency parameters for drugs such as phenytoin and propranolol which exhibit either saturable elimination kinetics or a capacity limited first pass effect. Mean Tmax, Cmax and area under the plasma-concentration time curve values from 0 to infinity (AUC 0-infinity) were compared after a single and multiple dose(s) of a test or reference drug. The aim was to determine if there were systematic changes in the limits of the single dose confidence interval at steady state that would limit the usefulness of confidence intervals following a single dose in accurately predicting bioavailability following multiple dosing. The 90 per cent confidence interval expressed as a percentage of the reference mean for Tmax, Cmax, and AUC 0-infinity showed model dependent changes from single to multiple dosing in response to the level of data error and changes in absorption. Changes in clearance also seemed to have a marked effect on the observed limits of the single and multiple dose confidence intervals especially for Cmax which showed a characteristic change in the intervals as a function of the clearance ratio. The model used to describe phenytoin had confidence intervals for Cmax and AUC 0-infinity from single to multiple dosing that were similar to that seen for the experimental data. However, the model predictions for Tmax confidence intervals following single and multiple dosing was at variance with the experimental data for formulations A and B. 相似文献
5.
Summary A new modification of microvenous anastomosis, which has increased patency rates while simultaneously decreasing the difficulty of the procedure, is presented in this paper. The primary purpose of this study was to compare the classical and the temporary stent techniques of microvenous anastomosis. Because of problems such as mixing and tangling of strings during insertion and tying of the last four sutures while applying the temporary stent technique, we decided to modify the procedure. The silastic tube was removed through an incision (venotomy), distant from the actual suture line. This modified technique and the other above mentioned techniques were carried out on rat femoral veins. The results indicate that this modification has increased patency rates, shortened the time of anastomosis and facilitated the procedure. 相似文献
6.
Severe myoclonic epilepsy (SMEI) or Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. Recently, we generated and characterized a knock-in (KI) mice with an SCN1A nonsense mutation that appeared in three independent SMEI patients. The SCN1A-KI mice well reproduced the SMEI disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygous knock-in mice, trains of evoked action potentials in inhibitory neurons exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. We further showed that in wild-type mice the Nav1.1 protein is expressed dominantly in axons and moderately in somata of parbalbumin (PV) – positive inhibitory interneurons. Our immunohistochemical observations of the Nav1.1 are clearly distinct to the previous studies, and our findings has corrected the view of the Nav1.1 protein distribution. The data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. These information should contribute to the understanding of molecular pathomechanism of SMEI and to develop its effective therapies. 相似文献
7.
Birgit T Priest Kenneth M Blumenthal Jaime J Smith Vivien A Warren McHardy M Smith 《Toxicon》2007,49(2):194-201
The tarantula venom peptides ProTx-I and ProTx-II inhibit voltage-gated sodium channels by shifting their voltage dependence of activation to a more positive potential, thus acting by a mechanism similar to that of potassium channel gating modifiers such as hanatoxin and VSTX1. ProTx-I and ProTx-II inhibit all sodium channel (Nav1) subtypes tested with similar potency and represent the first potent peptidyl inhibitors of TTX-resistant sodium channels. Like gating modifiers of potassium channels, ProTx-I and ProTx-II conform to the inhibitory cystine knot motif, and ProTx-II was demonstrated to bind to sodium channels in the closed state. Both toxins have been synthesized chemically, and ProTx-II, produced by recombinant means, has been used to map the interaction surface of the peptide with the Nav1.5 channel. In comparison, beta-scorpion toxins activate sodium channels by shifting the voltage dependence of activation to more negative potentials, and together these peptides represent valuable tools for exploring the gating mechanism of sodium channels. 相似文献
8.
Stefan I McDonough 《Toxicon》2007,49(2):202-212
Some of the most potent and specific inhibitors of voltage-gated calcium channels are peptide toxins that inhibit channel function not by occlusion of the channel pore, but rather by interfering with the voltage dependence and kinetics of channel opening and closing. Many such gating modifier toxins conform to the inhibitor cystine knot structural family and have primary sequence or functional mechanism similar to toxins that target voltage-gated sodium or potassium channels. This review introduces known gating modifiers of calcium channels, discusses the selectivity, binding sites, and mechanism of the toxin-channel interaction, and reviews the usefulness of these toxins as research tools and as the basis for novel calcium channel pharmacology and therapeutics. 相似文献
9.
M. W. Oram D. I. Perrett J. K. Hietanen 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1993,97(2):274-294
An investigation was made into the directional sensitivity of cells in the macaque anterior superior temporal polysensory region (STPa) to the motion of objects. The cells studied were sensitive to the presence of motion but showed little or no selectivity for the form of the stimulus. Directional tuning was not continuously distributed about all possible directions. The majority of cells were most responsive to motion in a direction within 15° of one of the three cartesian axes (up/down, left/right, towards/away). Tuning to direction varied in sharpness. For most (34/37) cells the angular change in direction required to reduce response to half maximal was between 45 and 70° (for 3/37 cells it was > 90°). The estimates of the directionality (median I
d = 0.97) of STPa cells was similar to that reported for posterior motion processing areas (the middle temporal area, MT, and the medial superior temporal area, MST). The tuning for direction (sharpness, distribution and discrimination) of the motion-sensitive STPa cells were found to be similar to the tuning for perspective view of STPa cells selective for static form of the head and body. On average the STPa responses showed a 100- to 300-ms transient burst of activity followed by a tonic discharge maintained at approximately 20% of the peak firing rate for the duration of stimulation. The responses of motion-sensitive STPa cells occurred at an earlier latency (mean 91 ms) than responses of cells selective for static form (mean 119 ms), but the time course of responses of the two classes of cell were similar in many other respects. The early response latency and directional selectivity indicate that motion sensitivity in STPa cells derives from the dorsal visual pathway via MT/MST. The similarity of tuning for direction and perspective view within STPa may facilitate the integration of motion and form processing within this high-level brain area. 相似文献
10.
John F. Scrymgeour-Wedderburn Carolyn A. Reith Keith T. Sillar 《The European journal of neuroscience》1997,9(7):1473-1482
The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co-activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid (APV) or by excluding Mg2+ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non-selective 5HT1a receptor agonist, 5-carboxamidotryptamine (5CT) and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT1, a selective 5HT1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage-dependent block of NMDA channels by Mg2+, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg2+ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage-dependent Mg2+ block. When the membrane potential was depolarized by ~20 mV via depolarizing current injection (to mimic the NMDA-induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg2+ saline. The results suggest that intrinsic, NMDA receptor-mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co-activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage-dependent block of the NMDA ionophore by Mg2+ through activation of receptors with 5HT1a-like pharmacology. 相似文献