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101.
Tomoaki Yuhi Akihiko Wada Ryuichi Yamamoto Masanobu Urabe Hiromi Niina Futoshi Izumi Toshihiko Yanagital 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(2):209-212
We have previously reported that in bovine adrenal chromaffin cells Ptychodiscus brevis toxin-3 (PbTx-3) does not alter the veratridine-induced 22Na influx when given alone, but increases the influx of 22Na when co-applied with either - or -scorpion venom (Wada et al. 1992). In the present study, we characterized [3H]PbTx-3 binding in bovine adrenal chromaffin cells. [3H]PbTx-3 binding was saturable, reversible and of high-affinity with an equilibrium dissociation constant (Kd) of 32.0±4.9 nmol/1 and a maximum binding capacity Bmax of 6.2 ± 1.2 pmol/4 × 106 cells (4.5 ± 0.9 pmol/mg cell protein). A Hill plot revealed the lack of cooperative interaction among the binding sites. Unlabelled PbTx-3 inhibited [3H]PbTx-3 binding with an IC50 of 31 nmol/l. However, tetrodotoxin, veratridine, - and -scorpion venom, or veratridine in combination with either - or -scorpion venom did not alter [3H]PbTx-3 binding. All these results suggest that PbTx-3 binds to a site (site 5) distinct from the previously known four toxin binding sites, which does not gate voltage-dependent Na channels by itself, but is specifically involved in the allosteric modulation of Na channels in adrenal medullary cells.
Correspondence to: A. Wada at the above address 相似文献
102.
103.
A. De Luca F. Natuzzi G. Lentini C. Franchini V. Tortorella D. Conte Camerino 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(6):653-661
The effects of the enantiomers of mexiletine were tested on sodium currents of frog skeletal muscle fibers recorded by means of the three vaseline gap voltage clamp method and compared with the effects produced by tocainide enantiomers. The R-( – ) mexiletine produced a tonic block of the sodium current, elicited by single depolarizing test pulses from the holding potential of – 100 mV to – 20 mV, with an IC50 of 43.9 ± 1 M, whereas the corresponding S-( + ) enantiomer produced the same effects at about twofold higher concentrations. A similar stereoselectivity was observed with tocainide enantiomers, but at about 5 fold higher concentrations. Both the R-( – ) and S-( + ) enantiomers of mexiletine and tocainide produced a further use-dependent block of sodium currents when the test pulse was applied repetitively at a frequency of 2 Hz. The use dependent behaviour led to a significant lowering of the IC50 values with respect to the tonic block but the eudismic ratios ([IC50S-( + )]/[IC50R( – )]) and the relative potency between mexiletine and tocainide were maintained. All the tested compounds produced a left shift of the steady state inactivation curves (h) , suggesting a high-affinity interaction with the inactivated sodium channels. Again a stronger potency of R-( – ) vs. S-( + ) enantiomers and of mexiletine vs. tocainide was observed. The excitability characteristics recorded from the semitendinosus muscle by the two microelectrode technique were modified by the tested drugs in agreement with their ability to block sodium current. Thus a concentration-related increase in the threshold current required to elicit an action potential was observed along with a decrease in the amplitude and a shortening of the latency of action potential and a decrease in the firing capability of the membrane. Again the R-( – ) isomers were more potent than the S-( + ) ones and mexiletine was more effective than tocainide. These data corroborate the presence of a stereospecific site for these drugs on adult skeletal muscle sodium channels. The constant eudismic ratios between the enantiomers during both tonic and use-dependent block suggest that the increase in the apparent affinity of the receptor during statedependent conformational changes of the channel does not enhance its stereospecificity. The decrease in effective concentration upon high frequency stimulation supports the potential usefulness of low doses of R-( – ) mexiletine in the treatment of the abnormal hyperexcitability of the myotonic muscles, with a likely reduction of unwanted side effects. 相似文献
104.
Electrophysiological effects of dridocainide on isolated canine,guinea-pig and human cardiac tissues
C. Pankucsi P. P. Nánási M. Hegedüs A. Kovács G. Szénási K. Szemerédi 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(5):520-528
The cellular electrophysiological effects of dridocainide (EGIS-3966), a novel class I antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibres and papillary muscle preparations obtained from humans and guinea-pigs. In each preparation, dridocainide (0.6–2 mol/l) decreased the maximum velocity of action potential upstroke (Vmax) in a frequency-dependent manner, although marked differences were observed in its effects in Purkinje fibre and ventricular muscle preparations. In canine Purkinje fibres, action potential duration measured at 50% and 90% of repolarization was decreased, while action potential duration measured at 10% of repolarization was increased by dridocainide. In addition, the plateau of the action potential was depressed by the drug. These changes in action potential configuration were not observed in guinea pig or human papillary muscles. The offset kinetics of the dridocainide-induced V
max block were different in Purkinje fibres and in ventricular muscle: the slow time constant of recovery of V
max was estimated to be 2.5 s in dog Purkinje fibre and 5–6 s in human and guinea-pig papillary muscle. In guinea-pig papillary muscle, the rate of onset of the V
max block was 0.15 and 0.2 per action potential in the presence of 0.6 and 2 mol/l dridocainide, respectively. Dridocainide also decreased the force of contraction in this preparation. On the basis of the present results, dridocainide appears to posess mixed class LC and LA properties, with LC predominance in human and guinea-pig ventricular muscle. Present results also indicate that results of conventional classification of class I drugs may depend on the parameters chosen, as well as on the preparation selected. 相似文献
105.
十二烷基硫酸钠在天然水体中的降解作用 总被引:1,自引:0,他引:1
本文研究了十二烷基硫酸钠在天然水体中的降解作用,结果表明十二烷基硫酸钠在天然水体中的降解主要依赖于微生物的降解。微生物最适降解条件为pH6.5~9.4和36℃左右。降解作用随温度升高(4~36.5℃)和微生物浓度增大而加快,用十二烷基硫酸钠预先驯化微... 相似文献
106.
本文报告了0.1%敌鼠钠盐配制成的不同毒饵在旅客列车上对急性灭鼠毒饵拒食残存鼠的杀灭试验效果。采用间隔投饵饱和投药法,投毒14天便有效地杀灭了旅客列车上对急性灭鼠毒饵拒食残存鼠,粉迹法考核灭效达100%。敌鼠钠盐配制的毒饵适口性好,灭效高,现阶段列车灭鼠中,仍有较好的应用价值。 相似文献
107.
The inhibitory effect of nitric oxide (NO) on carotid chemosensory responses to hypoxia has been attributed in part to an antidromic inhibition of chemoreceptor cells activity. However, NO may also modulate the activity of the primary sensory neurons because NO is produced in the soma of these neurons located in the petrosal ganglion. Since a population of petrosal neurons is selectively activated by acetylcholine (ACh), we studied the effects of NO-donor, sodium nitroprusside (SNP), and the NO-synthase inhibitor, Nomega-nitro-l-arginine methyl ester (l-NAME), on the responses evoked in the carotid sinus nerve (CSN) by ACh applied to the petrosal ganglion in vitro. ACh (1 microgram-1 mg) increased the frequency of action potentials recorded from the CSN in a dose-dependent manner. SNP (10-50 microM) reduced the sensibility and amplitude of the CSN response to ACh, although the maximal response appears less affected. The withdrawal of SNP from the superfusion medium increased the sensibility of the responses to ACh. l-NAME (1-2 mM) slightly increased the sensibility of the ACh-induced responses, effect that persisted after l-NAME withdrawal. These results suggest that NO may play a role as modulator in this autonomic primary sensory ganglion. 相似文献
108.
Extracellular 4-aminopyridine (4-AP), tetraethylammonium chloride (TEA) and quinine depolarized the neuropile glial cell membrane and decreased its input resistance. As 4-AP induced the most pronounced effects, we focused on the action of 4-AP and clarified the ionic mechanisms involved. 4-AP did not only block glial K+ channels, but also induced Na+ and Ca2+ influx via other than voltage-gated channels. The reversal potential of the 4-AP-induced current was -5 mV. Application of 5 mM Ni2+ or 0.1 mM d-tubocurarine reduced the 4-AP-induced depolarization and the associated decrease in input resistance. We therefore suggest that 4-AP mediates neuronal acetylcholine release, apparently by a presynaptic mechanism. Activation of glial nicotinic acetylcholine receptors contributes to the depolarization, the decrease in input resistance, and the 4-AP-induced inward current. Furthermore, the 4-AP-induced depolarization activates additional voltage-sensitive K+ and Cl- channels and 4-AP-induced Ca2+ influx could activate Ca2+-sensitive K+ and Cl- channels. Together these effects compensate and even exceed the 4-AP-mediated reduction in K+ conductance. Therefore, the 4-AP-induced depolarization was paralleled by a decreasing input resistance. 相似文献
109.
Jamme I Barbey O Trouvé P Charlemagne D Maixent JM MacKenzie ET Pellerin L Nouvelot A 《Brain research》1999,819(1-2):132-142
In a mouse model of focal cerebral ischaemia, we observed after 1 h of ischaemia, that the total Na+, K+-ATPase activity was decreased by 39.4%, and then did not vary significantly up to 6 h post-occlusion. In the sham group, the dose-response curves for ouabain disclosed three inhibitory sites of low (LA), high (HA) and very high (VHA) affinity. In ischaemic animals, we detected the presence of only two inhibitory sites for ouabain. After 1 h of permanent occlusion, the first site exhibited a low affinity while the second site presented an affinity intermediate between those of HA and VHA sites, which evolved after 3 h and 6 h of occlusion towards that of the VHA site. The presence of only two ouabain sites for Na+, K+-ATPase after ischaemia could result from a change in ouabain affinity of both HA and VHA sites (alpha2 and alpha3 isoforms, respectively) to form a unique component. Irrespective of the duration of ischaemia, the smaller activity of this second site accounted entirely for the loss in total activity. Surprisingly, no modifications in protein and mRNA expression of any alpha or beta isoforms of the enzyme were observed, thus suggesting that ischaemia could induce intrinsic modifications of the Na+, K+-ATPase. 相似文献
110.
S. T. Kaehler N. Singewald A. Philippu 《Naunyn-Schmiedeberg's archives of pharmacology》1999,359(6):460-465
The aim of the present work was to clarify whether differences exist between the release of endogenous serotonin in the locus
coeruleus of normotensive and hypertensive rats. The locus coeruleus was superfused with artificial cerebrospinal fluid (aCSF)
through a push-pull cannula and serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in the superfusate
by HPLC combined with electrochemical detection. Compared with normotensive Wistar-Kyoto (WKY) rats, the basal release rate
of serotonin in the locus coeruleus of spontaneously hypertensive rats (SHR) was increased more than twofold. Intravenous
infusion of noradrenaline (4 μg/kg min) increased mean arterial blood pressure to the same extent in hypertensive and normotensive
rats. The pressor response was associated with an increased serotonin release. In WKY rats, the release of serotonin in the
locus coeruleus evoked by noradrenaline infusion was more pronounced than in SHR. In WKY rats, intravenous infusion of sodium
nitroprusside (150 μg/kg min) led to a fall in blood pressure which was less pronounced and lasted shorter than in SHR. The
depressor response was associated with decreased serotonin release. In WKY rats, the decrease in serotonin release evoked
by sodium nitroprusside was more pronounced and lasted longer than in SHR. Neither noradrenaline nor sodium nitroprusside
influenced the outflow of 5-HIAA. The sensory stimuli noise and tail pinch led to a slight rise in arterial blood pressure
which was similar in WKY rats and SHR. These stimuli enhanced the release rate of serotonin and the outflow of 5-HIAA to the
same extent in the locus coeruleus of normotensive and hypertensive rats. The findings suggest that the enhanced release of
serotonin in the locus coeruleus of genetically hypertensive rats reflects a mechanism counteracting the disturbed blood pressure
homeostasis. Stressors influence blood pressure and release of serotonin in the locus coeruleus of SHR and WKY rats to the
same extent.
Received: 16 November 1998 / Accepted: 22 February 1999 相似文献