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1.
The effect of gamma-aminobutyric acid (GABA) on antidromically identified tubero-infundibular (TI) neurons was examined in hypothalamic slices of ovariectomized female rats. Twenty antidromically evoked spikes were obtained in the medial basal hypothalamus, including the arcuate and ventromedial nuclei, by electrical stimulation of the median eminence. Sixteen of them had a notch in the rising phase and fractionation of the initial segment (IS)- and somatodendritic (SD)-spikes was elicited by repeated stimulation at frequencies higher than 10 Hz. The application of 0.5-1.5 mM GABA to the incubation medium inhibited SD spikes in 7 of these 16 neurons. The latency, amplitude and threshold of IS spikes were not affected by GABA except for one spike whose latency fluctuated. On the remaining 9 neurons having the notch, no effect of 5-10 mM GABA was discernible. Four of 20 antidromically evoked spikes, which had a smooth rising phase and a shorter duration, were not inhibited by 5-10 mM GABA, but a fluctuation of the latency was observed in one neuron. Fifteen neurons having spontaneous unit activity were also obtained in the arcuate nucleus and its adjacent area and tested with GABA. In 10 of the 15 neurons, spontaneous unit activity disappeared following 0.1-1.5 mM GABA perfusion, while the firing rate in the remaining 5 neurons was not affected by 5-10 mM GABA. These results provide evidence for a direct inhibitory effect of GABA on TI neurons and support the involvement of GABAergic neurons in regulating neuroendocrine functions.  相似文献   

2.
A study was made of the time course and kinetics of [3H]GABA uptake by dispersed cell cultures of postnatal rat cerebellum with and without neuronal cells. The properties of GABA neurons were calculated from the biochemical difference between the two types of cultures. It was found that for any given concentration of [3H]GABA, or any time up to 20 min, GABA neurons in cultures 21 days in vitro had an average velocity of uptake several orders of magnitude greater than that of nonneuronal cells. In addition, the apparent Kmvalues for GABA neurons for high and low affinity uptake were 0.33 X 10(-6) M and 41.8 X 10(-4) M, respectively. For nonneuronal cells, the apparent Km for high affinity uptake was 0.29 X 10(-6) M. The apparent Vmax values for GABA neurons for high and low affinity uptake were 28.7 X 10(-6) mol/g DNA/min and 151.5 mmol/g DNA/min, respectively. For nonneuronal cells, the apparent Vmax for high affinity uptake was 0.06 X 10(-6) mol/g DNA/min. No low affinity uptake system for nonneuronal cells could be detected after correcting the data for binding and diffusion. By substituting the apparent kinetic constants in the Michaelis-Menten equation, it was determined that for GABA concentrations of 5 X 10(-9) M to 1 mM or higher over 99% of the GABA should be accumulated by GABA neurons, given equal access of all cells to the label. In addition, high affinity uptake of [3H]GABA by GABA neurons was completely blocked by treatment with 0.2 mM ouabain, whereas that by noneuronal cells was only slightly decreased. Most (75-85%) of the [3H]GABA (4.4 X 10(-6) M) uptake by both GABA neurons and nonneuronal cells was sodium and temperature dependent.  相似文献   

3.
The number of spikes which must be recorded in order to detect significant correlation between spike trains of two synaptically connected neurons was estimated by a mathematical model. Dependence of this number of spikes on importance of interneuronal connection (measured as the amplitude of the EPSP evoked by a single spike of the input neuron in the output cell) and on the intensity of total spontaneous excitatory influences on the output neuron and on its own parameters was studied. For cells which corresponded in the weight of connections between them, their intrinsic parameters, and characteristics of spontaneous activity to real spinal neurons, the necessary number of spikes was 107–108. An increase in amplitude of the single EPSP and also a decrease in the intensity of the input spontaneous spike train and parameters of after-hyperpolarization of the postsynaptic neuron led to a decrease in the number of spikes necessary for the detection of significant correlation. On the basis of the results of this and previous investigations the possible principles for construction of a spinal locomotor generator are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 3, pp. 290–296, May–June, 1980.  相似文献   

4.
Short-latency responses of single relay neurons of the lateral geniculate body to electrical stimulation of the optic tract were studied. The response of many neurons was complex and could consist of a series of (1–3) spikes with fixed latent periods. Each spike of such a response can be recorded on the EPSP in the absence of other spikes, preserving its latent period. The fixed latent periods of different relay neurons may vary from one to another. In the intervals between spikes with these latent periods active inhibition (IPSP) takes place. The series of spikes, EPSP, and IPSP is completed, as a rule, by a long IPSP.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 5, No. 1, pp. 28–32, January–February, 1973.  相似文献   

5.
GABA-T (4-aminobutyrate-2-ketoglutarate aminotransferase) has been found in human hair follicle. Kinetics experiments with hair follicle homogenate supported a ping-pong type of enzymatic mechanism. Extrapolated Km values were 1.02 mmol/l for GABA and 0.45 mmol/l for alpha-ketoglutarate. Hair follicle GABA-T activity was completely inhibited by preincubation of the samples with either 5 x 10(-8) mol/l aminooxyacetic acid or 5 x 10(-4) mol/l gamma-vinyl GABA. The radioenzymatic assay presented is both sensitive enough (only 10 hair follicles are needed for one assay) and economical, making it suitable for clinical practice. Hair follicle GABA-T activity determination could be useful in the study of GABA deficiency diseases (such as epilepsy), congenital GABA-T deficiencies or the control of GABA-T inhibitors treatment.  相似文献   

6.
γ-氨基丁酸对小白鼠离体胃标本胃酸分泌的促进效应   总被引:16,自引:0,他引:16  
为了探索γ-氨基丁酸(GABA)对小白鼠离体胃标本胃酸分泌(GAS)的影响及机制,在体外37℃缓冲液中培育离体、胃腔灌流并维持胃内12 cm水柱压力的全胃标本,用pHS-3型精密酸度计测定灌流液的pH。结果表明:γ-氨基丁酸(GABA)(1~10×10-7mol/L)和巴氯芬(Bac, 0.6~9.6×10-7mol/L)以一种浓度依赖的方式显著地促进胃酸分泌(GAS),而西咪替丁(Cim, 2~20×10-7mol/L)以一种浓度依赖的方式有力地抑制GAS。印防已毒素(Pic, 3×10-7mol/L)不影响基础胃酸分泌(BGAS)和GABA促进GAS的效应,而番氯芬(Phac, 0.6×10-7mol/L)能完全阻断GABA的促进效应。Cim不能完全消除GABA和Bac对GAS的促进效应。以上结果提示,在小鼠中GABA可以通过激活胃中GABAB受体促进离体胃标本的GAS,可能胃壁胆碱能神经元和非神经细胞,如壁细胞及某些内分泌细胞上都存在GABAB受体,GABA可直接或简接地剌激胃壁细胞分泌酸。  相似文献   

7.
Tan ZJ  Wei JB  Li ZW  Shao M  Hu QS  Peng BW 《生理学报》2000,52(5):381-384
在急性分离的大鼠背根神经节(dorsal root ganglion,DRG)细胞上,应用全细胞膜片箝技术观察了预知催产素(oxytocin,OT)对GABA激活电流的调制作用。结果如下:(1)大多数细胞(48/52,90.5%)对GABA敏感。(2)OT可引起51.3%(20/39)的受检细胞出现外向膜电流;43.6%(17/39)无明显膜反应;5.1%(2/39)出现内向膜电流。(3)预加OT  相似文献   

8.
On a preparation of isolated spinal cord of the frog Rana ridibunda, using intracellular recording from lumbar motoneurons, there were compared effects of GABA and Gly on membrane potentials, membrane resistance, and EPSP evoked by activation of dorsal root fibers or of brainstem reticular formation. All parameters were compared in the same cell. At the same concentration (10 mM), Gly evoked membrane depolarization by 20–50% greater than GABA. Response of application of a mixture of GABA and Gly was by 20% lower than the arithmetic sum of responses to the GABA application and the Gly application. The late components and the semiwidth both of complex and of simpler DR and RF EPSP decreased significantly (to 95%) on the background of application of GABA and Gly. The late components of the both EPSP were inhibited stronger by GABA than by Gly. The early mono- and disynaptic EPSP components were inhibited to the essentially lesser degree than the late components. Gly always inhibited the early DR EPSP more markedly than GABA did. In the greater part of motoneurons the early RF EPSP were stronger inhibited by Gly, in their smaller part, by GABA. In many motoneurons the early components did not decrease at all. The motoneuron membrane resistance decreased under effect of GABA and Gly to the approximately equal extent (by 10–30%). Not in all neurons there was revealed the correspondence between a decrease of the membrane resistance (RM) and a decrease of the early EPSP components. Based on the obtained data, it is suggested that the inhibitory influences in frogs is mediated by both Gly- and GABA-receptors. On the membrane of motoneuron the inhibition is mediated to the relatively greater degree by Gly-receptors, whereas on the membrane of interneurons, by GABA-receptors. During inhibition of DR EPSP the predominance of Gly-receptors is observed in the greater number of motoneurons than during inhibition of RF EPSP. Between individual motoneurons there are significant quantitative differences of all parameters.  相似文献   

9.
Topical application of the odorants guaiacol (10(-3) mol/l, 1-30 min) and 2-isobutyl-3-methoxypyrazine (IBMP, 10(-5)-10(-3) mol/l, 15 min) caused time- and concentration-dependent reductions in the secretory granule content of acinar cells of the superficial Bowman's glands (sBG) and moderate to extensive vacuolation in acinar cells of sBG and deep olfactory glands (dG). Topical application of 9.8 mg/ml scopolamine 10 min before 10(-4) mol/l IBMP significantly reduced the amount of secretory granule depletion from sBG compared to that seen with IBMP alone and resulted in less extensive vacuolation in sBG and dG acinar cells. The i.p. injection of 42 mg/kg propranolol 10 min before topical application of 10(-4) mol/l IBMP had no effect on the action of IBMP. Guaiacol and IBMP also had time- and concentration-dependent effects on the secretory activity of sustentacular cells in the olfactory epithelium. The protrusion of secretory material into the mucociliary matrix that covers the epithelial surface and vacuolation within the secretory material resulted from odorant application. Scopolamine and propranolol had no effects on the action of IBMP on sustentacular cell secretory activity. When applied in the vapor phase, guaiacol elicited action potentials recorded from individual olfactory receptor neurons; the impulse frequency was concentration-dependent and showed tonic and phasic components when the duration of stimulation was varied. Low to moderate concentrations of IBMP delivered in the vapor phase evoked monophasic negative slow voltage transients recorded from the surface of the olfactory mucosa. The amplitudes of these transients increased with increasing stimulus concentrations. Higher concentrations or longer stimulus durations evoked longer-latency positive-voltage generating processes and negative afterpotentials. The properties of the electrophysiological responses to both odorants were characteristic of responses evoked by a wide variety of 'typical' odorants.  相似文献   

10.
The effects of gamma-aminobutyric acid (GABA) have been studied on the synaptic depression, frequency facilitation, and posttetanic potentiation (PTP) of a unitary, monosynaptic, and presumably cholinergic excitatory postsynaptic potential (EPSP). This EPSP, produced by minimal stimulation of the right visceropleural connective, was recorded in cell R 15 of Aplysia californica. Perfusion with GABA (10(-4)-10(-3) M) reduces the size of all EPSPs produced by a train of 100 stimuli at 1/s. It also reduced the synaptic depression and PTP, and increases the frequency facilitation seen during the train. GABA does not significantly effect the membrane resistance (mean 102%) but it slightly depolarizes (mean 6 mV) the postsynaptic cell. GABA does not reduce an acetylcholine iontophoretic potential produced on R15. The effects of GABA are reduction when chloride is replaced by acetate but they remain significant. Picrotoxin and bicuculline fail to antagonize GABA. Addition of sodium azide or dinitrophenol does not reduce the action of GABA and even prolongs it. The effects of GABA are attributed to two sites of action: a postsynaptic one, responsible for the small change in potential and partially responsible for the reduction of EPSP size; and a presynaptic one, responsible for a further reduction of EPSP size and the changes of depression, facilitation, and PTP.  相似文献   

11.
Adult males of Estigmene acraea use pyrrolizidine alkaloids to produce pheromones and all stages probably use pyrrolizidine alkaloids for defense. The alkaloids are obtained from plants by the caterpillars. We demonstrate that a contact chemoreceptor neuron in the lateral galeal sensillum exhibits a dose-dependent response to seneciphylline N-oxide, a widely occurring pyrrolizidine alkaloid, down to concentrations of 10(-9) x mol l(-1), and even at 10(-12) x mol l(-1) the response is greater than to salt alone. At concentrations of 10(-6) mol x l(-1) and above the instantaneous firing rate is very high, and at 10(-4) mol x l(-1) initially exceeds 500 spikes s(-1). The firing rate declines in the 200 ms following stimulus onset but then is sustained with an instantaneous firing rate in excess of 100 spikes s(-1) for at least the next 800 ms. At lower concentrations a delay occurs before firing is initiated, and then the pattern of firing is irregular. The cell is equally sensitive to some but not all of several other pyrrolizidine alkaloids tested as free bases and their N-oxides. It also responds to ouabain, which may also serve as a defensive compound, and to asparagine and fructose but with much higher thresholds than to the pyrrolizidine alkaloids.  相似文献   

12.
可乐定对背根神经节神经元GABA激活电流的抑制作用   总被引:6,自引:1,他引:5  
Wang QW  Li Q  Li ZW 《生理学报》1998,50(1):19-27
本实验在新鲜分离大鼠背根神经节(DRG)细胞上应用全细胞膜片的箝记录研究贤上腺素α2-受体激动剂可乐定(clonidine)对GABA-激活电流的调制作用。发现缘大多数DRG细胞对GABA(10^-6 ̄10^-3mol/L)敏感(72/75),产生浓度依赖性的内向电流;并且可被bicuculine(10^-5 ̄10^-4mol/L)所阻断。在多数细胞中(51/72)预加可乐定(10^-8 ̄10^-  相似文献   

13.
非洲爪蟾卵母细胞GABAB和GABAc受体介导的电流反应   总被引:4,自引:0,他引:4  
Yang Q  Li ZW  Wei JB 《生理学报》2001,53(4):311-315
实验应用双电极电压箝技术,在具有滤泡膜的非洲爪蟾(Xenopuslaevis)卵母细胞上记录到γ-氨基丁酸(γ-aminobutyricacid,GABA)-激活电流。此GABA-激活电流的特点及有关GABA受体类型的研究和分析如下(1)在35.5%(55/155)的受检细胞外加GABA可引起一慢的浓度依赖性的外向电流。(2)GABAA受体的选择性拮抗剂bicuculline(10  相似文献   

14.
The prolonged effect of thyroliberin in ULD after single intramuscular injection on contractility of lymphatic vessels directly was investigated. The controlled group of animals received injection of 0.2 ml of physiological solution. The experimental group was injected by 0.2 ml of thyroliberin in concentrations of 10(-10) or 10(-16) mol/l (1 x 10(-4) and 1 x 10(-10) micrograms/kg of the body weight respectively). During the experiment the animals were grouped in the following way: 1) directly after the injection; 2) 3 hours later; 3) on the 1st day and then every day during 2 weeks. Lymphatic vessels reactivity of the experimental animals as well as controlled was studied by application of thyroliberin and noradrenalin (in concentrations of 1 x 10(-16) and 1 x 10(-6) mol/l respectively) directly on mesentery lymphatic vessels. The lymphatic vessels reaction in control group of animals on the noradrenalin and thyroliberin was the same during the period of observation. Thyroliberin stimulated contractility at concentration of 1 x 10(-16) mol/l. The reaction of experimental group was dramatically decreased to 10(-4) mol/l on the 1st and the 3rd day (in the case i.m. injected concentration 1 x 10(-10) mol/l) and to 10(-10) mol/l (in the case of i.m. injected concentration 10(-16) mol/l). The lymphatic vessels reactivity to exogenous thyroliberin gradually established at the 6-7th days till 12th day from the moment of thyroliberin injection. The mechanisms of the action of thyroliberin in ULD are discussed.  相似文献   

15.
In calmodulin depleted membranes from human erythrocytes, the Ca2+-dependent phosphatase showed different sensitivity to calmodulin and ATP with variable affinity towards free calcium concentrations: a calmodulin-dependent activity with high calcium affinity, K1/2 = 1.2 X 10(-7) mol/l calcium, that was fully activated at submicromolar calcium concentrations, higher concentrations being rather inhibitory; an ATP-dependent activity with lower calcium affinity, K1/2 = 10(-6) mol/l calcium, that was fully activated at 10(-5) mol/l calcium in the presence of 50-200 mumol/l ATP and was insensitive to calmodulin, and a calcium dependent phosphatase that was active at a wider ranger of free calcium, 10(-8)-10(-5) mol/l, and required the presence of both calmodulin and ATP.  相似文献   

16.
In the present study, we explored the effect of the progestin medrogestone on the sulfatase and sulfotransferase activities in the hormone-dependent MCF-7 and T-47D human breast cancer cell lines. After 24 h incubation at 37 degrees C of physiological concentrations of estrone sulfate ([3H]-E1S: 5x10(-9) mol/l), it was observed that this estrogen was converted in a great proportion to E2 in both cell lines. Medrogestone significantly inhibits this transformation, at all the concentrations tested (5x10(-8) to 5x10(-5) mol/l), in both cell lines. The IC50 values were 1.93 micromol/l and 0.21 micromol/l in MCF-7 and T-47D cells, respectively. In another series of studies, after 24 h incubation at 37 degrees C of physiological concentrations of estrone ([3H]-E1: 5x10(-9) mol/l), the sulfotransferase activity was detectable in both cell lines. Estrogen sulfates (ES) are found exclusively in the culture medium, which suggests that as soon as they are formed they are excreted into the medium. Medrogestone has a biphasic effect on sulfotransferase activity in both cell lines. At low doses: 5x10(-8) and 5x10(-7) mol/l, this compound stimulates the enzyme by +73.5 and 52.7%, respectively, in MCF-7, and by 84.5 and 62.6% in T-47D cells. At high concentrations: 5x10(-6) and 5x10(-5) mol/l, medrogestone has no effect on MCF-7 cells, but inhibits the sulfotransferase activity in T-47D cells by -31.4% at 5x10(-5) mol/l. In conclusion, the inhibitory effect provoked by medrogestone on the enzyme involved in the biosynthesis of E2 (sulfatase pathway) in estrogen-dependent breast cancer, as well as the stimulatory effect on the formation of the inactive ES, support a probable anti-proliferative effect of this progestin in breast tissue. Clinical applications of these findings can open new therapeutic possibilities for this disease.  相似文献   

17.
Input-output relation were of giant neurons of a marine mollusc, Onchidium verruculatum, and a computer-simulated neuron investigated in terms of microstructure of nerve impulse train. The microstructure of input impulse train, the size of a unitary EPSP, and the extent of spontaneous firing activity of a single neuron had an important influence upon the effective summation of arriving synaptic inputs, the elicitation of output spikes, and intervals between succeeding output spikes. The neuron responded differently to respective input trains with different time structures, i.e. it discriminated input time pattern to various degrees. The manner in discrimination of input time pattern was dependent on the size of the unitary EPSP and the extent of the spontaneous firing activity, if it had. Some discussions were made with regard to possible coding systems of neural signal, assuming a frequency code and/or a pattern code.  相似文献   

18.
Using halothane-anaesthetized cats implanted with push-pull cannulae, we investigated the effects of GABA application into the VM/VL on the release of [3H] DA continuously synthetized from [3H] tyrosine in the ipsilateral CN and SN and on single unit activity of nigral DA cells. GABA was applied (30 min) at a concentration of 10(-3) or 10(-5) M since the higher concentration reduces the local multi-unit activity in the VM/VL while the opposite response is observed with the lower one. The application of GABA into the VM/VL at a concentration of 10(-3) M resulted in an increase in nigral [3H] DA release, an inhibition of DA cell firing and a decrease in [3H] DA release in the CN. The latter effect is likely due to the inhibition of DA neuron activity which is triggered through DA autoreceptors by DA released from dendrites. In contrast, when applied at a concentration of 10(-5) M into the VM/VL, GABA stimulated [3H] DA release in the CN despite its inhibitory effect on single unit activity of DA cells. Furthermore, the nigral release of [3H] DA was no longer affected. These results indicated that DA release from nerve terminals was not dependent on nerve activity and they favour the existence of a potent facilitatory presynaptic regulation of DA release. The intervention of a presynaptic mechanism was further established by examining the effect of GABA (10(-5) M) application into the VM/VL on [3H] DA release in the CN shortly after a complete ipsilateral hemisection of the brain made at the meso-diencephalic level.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

19.
The effect of Cd2+, as one of the most widespread toxic environmental pollutants, was studied on gamma-aminobutyric acid (GABA) evoked responses of identified neurons in the central nervous system of the pond snail, LYmnaea stagnalis L. (Gastropoda). In the experiments, the modulation of the action of GABA both on neuronal activity (current clamp recording) and on the a GABA activated membrane Cl- current (voltage clamp studies) has been shown. It was found that: 1. GABA could evoked three different various types of response in GABA sensitive neurons: i) hyperpolarization with strong inhibition of ongoing spike activity, ii) short depolarization with an increase of spike the activity, iii) biphasic respone with a short excitation followed by a more prolonged long inhibition. 2. In low-Cl- solution the inhibitory action of GABA was reduced or eliminated, but the excitatory one was not or only moderately affected. 3. CdCl2 inhibited the GABA evoked hyperpolarization, but left intact or only slightly reduced the excitation evoked by GABA. 4. The inward Cl- current evoked by GABA at a -75 mV holding potential was slightly augmented in the presence of I micromol/l Cd2+, but was reduced or blocked at higher cadmium concentrations. The effect of Cd2+ was concentration and time dependent. 5. Parallel with reducing the GABA evoked current, cadmium increased both the time to peak and the half inactivation time of the current. 6. CdCl2 alone, in 50 micromol/l concentration, induced a 1-2 nA inward current. The blocking effect of cadmium on GABA activated inhibitory processes can be an important component of the neuro-toxic effects of this heavy metal ion.  相似文献   

20.
Vlkolinský R  Stolc S  Ross A 《Life sciences》1999,65(18-19):1969-1971
Reactive oxygen species have been suggested to participate in the impairment of nervous tissue by oxidative stress, induced by hypoxia (HYP) followed by reoxygenation (ROX). Although the mechanisms of such injury are rather complex, antioxidants might exert some protective action under such circumstances. This study tested the effect of a series of compounds interfering with the generation and action of reactive oxygen species on impairment of synaptic transmission in the CA1 region of rat hippocampal slices exposed to HYP followed by ROX in vitro. Shortlasting HYP (typically 4.5-7.5 min under the conditions used) resulted in fast decay of the amplitude of population spikes evoked in the CA1 neurons by stimulation of Sch?ffer collaterals. The impairment was mostly irreversible. However, in the presence of the antioxidants stobadine, 21-aminosteroid U-74389G, melatonin and trolox (with optimal concentrations of 10-30 micromol/l, 10 micromol/l, 30-100 micromol/l and 200 micromol/l, respectively), the irreversible damage of the transmission was significantly diminished. The decay of the synaptic transmission failure during HYP was also delayed by stobadine, U-74389G and melatonin. The results demonstrated that compounds with antioxidant activity may effectively protect nervous tissue during HYP and ROX.  相似文献   

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