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1.
Effects of adenosine and adenosine analogues on spontaneous contractility of the human fallopian tube during different phases of the menstrual cycle were studied. In isthmic preparations, a stimulatory effect by L-N6-phenylisopropyladenosine (L-PIA), with preference for adenosine A1-receptors, was seen mainly during the proliferative phase. In ampullary preparations, stimulation by L-PIA was seen both in the secretory and proliferative phases. Adenosine and 2-chloroadenosine exerted similar stimulatory effects. 5'-N-ethylcarboxamide-adenosine (NECA), with selectivity for adenosine A2-receptors, or D-PIA never showed a stimulatory effect. At concentrations above those needed for stimulation, adenosine, 2-chloroadenosine and L-PIA inhibited spontaneous contractions, in common with NECA and D-PIA. Here, NECA was more potent than L-PIA. The D-PIA and L-PIA were equipotent. The inhibition was seen during the whole menstrual cycle. The competitive adenosine antagonist 8-p-sulphophenyltheophylline (PS?T) reversibly antagonized the stimulatory and inhibitory effects elicited by adenosine and the analogues. The PS?T alone could exert a stimulatory or an inhibitory action on spontaneous contractility. We suggest that adenosine can modulate contractile activity in the human fallopian tube via stimulatory A1-and inhibitory A2-receptors. These receptors are located on the smooth muscle cells, and might act via cAMP. The relative receptor dominance may be influenced by cyclic hormonal changes.  相似文献   

2.
The receptors involved in adenosine-induced modulation of cholinergic neuroeffector transmission in guinea-pig ileum were explored by means of the non-selective stable analogue, 2-chloroadenosine and analogues with preference for AI receptors, L-N6-phenylisopropyladenosine (L-PIA), and A2 receptors, 5'-N-ethylcarboxamideadenosine (NECA) and D-N6-phenylisopropyladenosine (D-PIA). 2-chloroadenosine, L-PIA and NECA were equipotent in inhibiting contractile responses to nerve stimulation, whereas D-PIA exerted a similar activity only in high concentrations. The release of acetylcholine induced by nerve stimulation was inhibited to a similar degree by NECA, L-PIA and D-PIA. The phosphodiesterase inhibitor, ZK 62.7II, and the activator of adenylate cyclase, forskolin, enhanced the inhibitory effect of NECA, but not that of L-PIA, on contractile responses to nerve stimulation. Only NECA inhibited contractions induced by direct muscle stimulation and ZK 62.7II enhanced this inhibition. It is concluded that adenosine inhibits the neuroeffector transmission in guinea-pig ileum mainly by a prejunctional, cAMP-independent, mechanism, involving AI receptors and a supplementary activation of post-junctional A2 receptors. In addition there may be a prejunctional inhibitory effect of high agonist concentrations, exerted via A2 receptors and influenced by the prevailing levels of cAMP.  相似文献   

3.
The activity of 52 single auditory units in the central nucleus of the inferior colliculus (IC) was recorded along with cortical and hippocampal (CA1) electrograms and neck muscle electromyograms in behaving, head-restrained guinea pigs during paradoxical sleep (PS) and wakefulness. Sixteen (30%) of the IC auditory units showed positive correlation with the hippocampal theta () rhythm: 8 (15%) were rhythmic with phase-locking (type 1), 8 (15%) showed only phase-locking with no rhythmicity (type 2), while 70% did not show any correlation to hippocampal rhythm (type 3). During wakefulness IC neurons (4 of 13) showed a higher synchrony with hippocampal when sound-stimulated at the unit's characteristic frequency. During PS all IC auditory neurons recorded presented some hippocampal correlation: 40% were rhythmic and phase-locked to the frequency and 60% were nonrhythmic maintaining the phase-locking. Shifts in the angle of phase-locking to the rhythm were observed during PS. It is suggested that the hippocampal rhythm may play the part of an internal clock, adding a temporal dimension to the processing of auditory sensory information.  相似文献   

4.
Summary On the basis of spontaneous firing patterns and relations to the hippocampal theta rhythm, three cell types were identified within the medial septal nucleus and vertical limb of the nucleus of the diagonal band of Broca (MSN-NDB). In addition to the well known rhythmically bursting cells that fired in bursts on each cycle of the hippocampal theta rhythm, two other cell types are distinguished. Clock cells fired at high rates with a very regular, periodic firing pattern that was unrelated to the theta rhythm. Irregular cells fired at much lower rates, especially during theta rhythm, and had a pseudo-random firing pattern. The firing of irregular cells was often significantly phase-locked to the hippocampal theta rhythm. Crude estimates of the relative proportions of these cell types suggest that the rhythmically bursting cells comprise about 75% of the cells of the MSN-NDB. These three cell types bear a remarkable resemblance, in firing patterns and relative proportions, to the three principal cell types of the medial septal nuclei described in the freely moving rat (Ranck 1976). Measurements of the preferred phases of firing of 128 rhythmically bursting septal neurons (including 22 atropine-resistant and 11 atropine-sensitive cells) indicate that there is no single preferred phase of firing for the population. Rather the distribution of phases over the theta cycle is statistically flat. Variations in recording locations cannot account for this distribution since large differences in preferred phase were found for pairs of cells at the same location. Similarly, plotting only the group of cells identified as projection cells by antidromic activation from the fimbria/fornix, failed to reveal a peak in the distribution. In contrast to the rhythmically bursting cells, the distribution of preferred firing phases for the irregular cells with a significant phase-locking to the theta rhythm did have a clear peak. The peak occurred near the dentate theta rhythm positivity, consistent with the hypothesis that they are driven by feedback from CA1 complex-spike cells.  相似文献   

5.
6.
Neuronal isolation of the rabbit cerebral hemisphere shifts the EEG spectrum in the direction of slower processes. Application of acetylcholine to the cortex brings about EEG activation and appearance of the theta rhythm. Initially serotonin application is accompanied by the appearance of theta rhythm periods; during subsequent administration of the drug these periods are gradually substituted by slow delta waves. Combined application of serotonin and acetylcholine to the isolated cortex brings about bursts of high amplitude activity, abruptly substituted by silent phases. In contrast to the intact cortex, where serotonin brought about prolonged and rhythmic alternation on the EEG of phases of high amplitude activity and of silent periods, in the isolated cortex the bursts of activity of about 1 min duration appeared only after application of acetylcholine to the serotonin-saturated cortex. Repeated phases of activation were either absent or of short duration and were rapidly extinguished.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 35, No. 3, pp. 733–741, July–August, 1985.  相似文献   

7.
Summary The activity of 72 neurons recorded in the reticularis pontis oralis nucleus (RPO) was examined in anesthetized and curarized rats during hippocampal theta () rhythm elicited by either sensory stimulation or carbachol microinjections. During hippocampal rhythm evoked by sensory stimulation, 63.9% of RPO neurons increased their discharge rate while the firing rate decreased in 20.8%. In all cases, the RPO neurons maintained a non-rhythmic discharge pattern. In 44% of the neurons the discharges tended to occur on the positive wave of the rhythm. Similar firing patterns were seen in 18 RPO neurons recorded during rhythm elicited by both, sensory stimulation and a carbachol microinjection; this effect was blocked by atropine. These results indicate that the RPO region contributes to the generation of hippocampal rhythm with a tonic and nonrhythmic outflow through a cholinergic system which may be muscarinic.  相似文献   

8.
Summary The firing of neurons from layers II and III of medial entorhinal cortex (MEC) was examined in relation to the hippocampal theta rhythm in urethane anesthetized and walking rats. 1) MEC neurons showed a significant phase relation to the hippocampal theta rhythm in both walking and urethane anesthetized rats, suggesting that this region contributes to the generation of both atropine-resistant and atropine-sensitive theta rhythm components. 2) The proportion of phase-locked cells was three times greater in walking rats (22/23 cells) as compared to anesthetized rats (8/23 cells), indicating that MEC cells made a greater contribution during walking theta rhythm. This difference was also manifest in the greater mean vector length for the group of phase-locked MEC cells during walking: 0.39 ± 0.13 versus 0.21 ± 0.08. Firing rate differences between walking and urethane conditions were not significant. 3) In walking rats, MEC cells fired on the positive peak of the dentate theta rhythm (group mean phase = 5°; 0° = positive peak at the hippocampal fissure). This is close to the reported phases for dentate granule and hippocampal pyramidal cells. The distribution of MEC cell phases in urethane anesthetized rats was broader (group mean phase = 90°), consistent with the phase data reported for hippocampal projection cells.These findings suggest that medial entorhinal neurons are the principal determinant of theta-related firing of hippocampal neurons and that their robust rhythmicity in walking as compared to urethane anesthesia accounts for EEG differences across the two conditions.  相似文献   

9.
Dorsal hippocampal theta rhythm () and extracellular unit activity from CA1 pyramidal layer were recorded in awake guinea pigs, both during standing and during walking on a conveyor belt at increasing speeds. Amplitude, frequency and rhythmicity of increased linearly with the movement speed. In this preparation we found the same three types of unit discharge patterns that have been described in anesthetized rats in the presence of spontaneous or induced hippocampal : type 1, rhythmic at frequency and phase-locked with ; type 2, discharging non-rhythmically but phase-locked with ; and type 3, discharging at random. Furthermore, all units modified their firing pattern when the animals walked, either by increasing their rhythmicity and/or phase-locking with or by increasing their firing frequency. During walking, some type 3 units changed into type 2 or type 1, type 2 units changed to type 1, and type 1 increased their rhythmicity. Consequently, the unit discharge rhythmicity and phase-locking with increased with the speed of movement. The mean rate of neuronal discharges increased linearly as a function of walking speed. In this paper we show that the progressive spectral changes determined by the intensity of movement are concomitant with the increase in rhythmicity of hippocampal cells. Moreover, the firing rate of these cells, and the amplitude, frequency and rhythmicity of , increased linearly as a function of walking speed, suggesting that neuronal excitation may be basically responsible for these changes in properties.Deceased  相似文献   

10.
We have investigated the type of purine receptor in the guinea-pig olfactory cortex, using pial surfaces slices maintained in vitro. Adenosine (0.1 to 100 mumol/l) bath applied in the presence of the uptake inhibitor nitrobenzylthioinosine, depressed the evoked potentials in a dose related fashion. Synthetic and uptake resistant adenosine analogues had the same effect as adenosine and the order of potency of these was: 5'-N-ethylcarboxamide adenosine greater than L-N6-phenylisopropyl adenosine (L-PIA) = N6-cyclohexyladenosine = 2-chloroadenosine greater than adenosine greater than D-N6-phenylisopropyladenosine (D-PIA). The D-stereoisomer of PIA was 45 times less potent than L-PIA. The methylxanthine compounds 8-phenyltheophylline (3 mumol/l) and 3-isobutyl-1-methylxanthine (50 mumol/l) antagonised the depression produced by L-PIA. Rolipram, a phosphodiesterase inhibitor, in concentrations up to 100 mumol/l had no effect on the evoked potentials or on adenosine action. Forskolin, a cAMP stimulant, slightly increased the amplitude of the evoked potential, and partly reversed the depressant effect of adenosine. Noradrenaline had no effect either alone or in the presence of adenosine. The results of these experiments indicate the existence of A1 subtype adenosine receptors in the guinea pig olfactory cortex probably linked to a depression of intracellular cAMP.  相似文献   

11.
Summary Most hippocampal formation single units in freely behaving rats fall into one of two categories (Ranck 1973). The most obvious behavioral correlate of complex-spike (CS) cells is spatially selective discharge (O'Keefe and Dostrovsky 1971), while theta cells show increased firing in phase with the EEG rhythm associated with Vanderwolf's Type I behaviors (e.g. walking, exploration). Recently, Colom and Bland (1987) described, in urethane anesthetized animals, a class of non-CS cell which was inactive in the presence of EEG and discharged continuously during LIA. They called these theta-off cells and used the term theta-on to refer to the classical theta cell. We describe the behavioral correlates of 14 theta-off cells encountered in CA1 (n = 1), hilus fascia dentata (FD; n = 4), subiculum (n = 6), and entorhinal cortex (n = 3). These cells were encountered very infrequently in the course of several experimental investigations of mature young and old rats involving 885 hippocampal neurons recorded from 33 rats during radial maze performance. Fourteen theta-on cells encountered within a few hundred microns of the sites where theta-off cells were recorded were included for comparison. Both theta-on and theta-off cells discharged single spikes and did not show CS bursting characteristic of pyramidal cells. Theta-off cells, however, exhibited significantly greater spike durations than theta-on cells. Mean rates for theta-on and theta-off cells were 8.7 Hz and 6.5 Hz, respectively. Maximum rates were 114 Hz and 104 Hz, respectively. Some cells of both types showed 6–8 Hz modulation while animals traversed the maze. Whereas firing rate for theta-on cells increased smoothly with running velocity, it decreased smoothly for theta-off cells. While no theta-on cells exhibited clear spatial selectivity, two hilar theta-off cells did. When EEG rhythm was temporarily abolished by local injection of tetracaine into the medial septum, two theta-off cells were observed to fire continuously at high rates irrespective of behavior, with a pronounced 18–20 Hz rhythmic modulation. Under these circumstances, theta-on cells decrease their rates. Within the 7 theta-off cells recorded in each of the two age groups, there were no statistically significant differences in firing characteristics. Possible anatomical candidates for theta-off cells are considered.  相似文献   

12.
Transmembrane potentials from medial septal and diagonal band of Broca (MS-DBB) neurons and hippocampal field activity were recorded in curarized and urethanized rats. MS-DBB cells were studied during large amplitude irregular activity and during hippocampal rhythm, elicited by either sensory (i.e. stroking the fur on the animal's back) or electrical stimulation of the reticularis pontis oralis nucleus (RPO). Three types of cells were described according to their firing pattern and the characteristics of their intracellular rhythm. Type A neurons displayed continuous rhythmic oscillations in the membrane potential (Vm) of approximately 17 mV. These oscillations generated rhythmic high-frequency spike trains which were phase-locked with hippocampal rhythm. Type A cells revealed intracellular rhythm even in the absence of hippocampal rhythm, suggesting that the activity of this type of cell was the most important in hippocampal genesis. Type B cells were characterized by marked postspike afterhyperpolarization and intracellular oscillations of smaller amplitude than in type A cells. Type C cells revealed a post-spike afterdepolarization and a lower amplitude, intracellular rhythm only in the presence of hippocampal rhythm. Type C neurons could fire slow spikes at depolarizing (46% of cells) or hyperpolarizing (15% of cells) Vms. Type B and C cells were intracellularly stained with Lucifer yellow. Although type B and C neurons revealed dissimilar electrophysiological properties, they had comparable morphological shapes. RPO electrical stimulation generated hippocampal rhythm and intracellular rhythm in types A and B cells but not in type C cells, and increased the spike rate in type C neurons. Electrical stimulation of the fornix only evoked synaptic responses in type B and C neurons, with antidromic responses being elicited in 12% of type C cells. These results indicate that probably most of the type A rhythmic cells did not receive direct hippocampal feedback and that at least some type C cells were projecting neurons. The present findings demonstrate that rhythm oscillations in the Vm of MS-DBB neurons elicit different rhythmic discharge patterns.  相似文献   

13.
Summary Intracellular recordings were made from hippocampal pyramidal cells identified by their depths and their responses to commissural stimulation. Recordings were made during spontaneous bouts of hippocampal theta rhythm in urethane anesthetized rats. Membrane potentials (V m) of pyramidal cells varied with the phase of the theta rhythm, that is, there was an intracellular theta rhythm. The changes in V m averaged about 2 mV peak to peak. Averaged intracellular theta waves showed that CA1 pyramids were most depolarized at the time of the positive peak of the extracellular theta rhythm recorded in (and superficial to) the CA1 pyramidal cell layer (CA1 theta). Peak depolarizations for CA3/4 pyramids were more broadly distributed, but occurred mainly in the interval just before the positive peak to just before the negative peak of the CA1 theta. Input impedance minima that were measurable at frequencies as high as 100 Hz occurred at about the same phases of the extracellular theta rhythm as the peak depolarizations (positive-going zero crossing to negative-going zero crossing of the CA1 theta). Such impedance changes imply conductance changes on the soma. The magnitude and localization of the conductance changes suggests that somatic IPSPs make major contributions to the intracellular theta rhythm. The phase relation between the intracellular and extracellular theta rhythms could be reversed by long duration current pulses that depolarized the cells slightly. This implies that either the intracellular theta-related IPSPs are depolarizing potential changes, or that they occur simultaneously with EPSPs. The phase of the intracellular theta rhythm was generally unaffected by long duration hyperpolarizing current pulses. Chloride leakage that reversed the evoked IPSPs usually had no effect on the phase of the intracellular theta rhythm, although in one case it appeared to cause its amplitude to increase.  相似文献   

14.
Interleukin-8 (IL-8), C5a and N-formyl-methionyl-leucyl-phenylalanine (fMLP) are chemotactic peptides with predominant effects on leukocytes during inflammation. With emphasis on C5a we studied the regulation of the production of IL-8 by human umbilical vein endothelial cells (HUVEC) in vitro. Primary HUVEC cultures were incubated with IL-1, TNF, C5a and fMLP for 24 h and 48 h prior to measurement of IL-8 in supernatants of the cells by an enzyme immunoassay. Whereas IL-1 and TNF significantly increased the levels of IL-8, C5a decreased the IL-8 production after 48 h. In addition, the ability of IL-1, TNF, C5a, fMLP and IL-8 to induce cell proliferation was compared by means of a 3H-thymidine incorporation assay. In contrast with IL-1 and TNF, both C5a and fMLP increased cell proliferation of HUVEC. This increase occurred with increasing concentrations of C5a contrary to IL-8, which showed increased cell proliferation at low, but not high IL-8 concentrations.  相似文献   

15.
Summary The firing of lateral septal neurons was examined in relation to the hippocampal theta rhythm in urethane anesthetized rats. In general, the firing rates of these cells were low during both theta and non-theta EEG states. There was no significant change in firing rate between the two states (theta: 8.5±9.9 spks/sec; non-theta: 6.0±5.3). Sixty-four of 68 cells fired simple spikes and 4 cells were found to fire bursts of action potentials (complex-spikes). Approximately 30% (21/65) of the cells showed a significant phase relation to the hippocampal theta rhythm. The preferred phases of firing of these 21 cells were broadly distributed. The possibility that the phase-locked firing of LSN cells is due to the phase-locked firing of hippocampal projection cells is discussed.  相似文献   

16.
Adenosine exerts effects via receptors of the AI- and A2-subtype. L-phenylisopropyl adenosine (L-PIA) is more potent than N-5'-ethylcarboxamido adenosine (NECA) at the A1-subtype receptor whereas the potency order is reversed at the A2-subtype receptor. Adenosine analogues have been shown to decrease blood pressure and heart rate and to induce a marked hypothermia. In the present series of experiments adenosine, L-PIA and NECA were given i.p. or i.v. to rats, and blood pressure, ECG and colonic temperature were recorded. The NECA was the most potent of the compounds in reducing blood pressure (EC50 2 micrograms kg-1 i.v.), followed by L-PIA (EC50 approximately 30 micrograms kg-1 i.v.) and adenosine (EC50 approximately 300 micrograms kg-1 i.v.). In contrast, L-PIA and NECA were equally active in reducing heart rate (EC50 approximately 6 micrograms kg-1 i.v.). and considerably more potent than adenosine (EC50 approximately 300 micrograms kg-1 i.v.). It is suggested that simultaneous measurement of blood pressure and heart rate could be a simple in vivo model for comparison of A1- and A2-receptor subtype mediated effects. Colonic temperature was markedly reduced after i.p. administration of the adenosine analogues. Thus, 100 micrograms NECA kg-1 reduced colonic temperature from 37.8 to 26 degrees C. A 5 degrees C temperature drop was obtained by 10 micrograms kg-1 NECA, by 200 micrograms kg-1 L-PIA and by 200 mg kg-1 adenosine. The fall in colonic temperature was associated with a loss of muscular activity, as determined by needle electrodes or by palpation, indicating an inhibition of shivering.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

17.
Summary The laminar distribution of theta () field potentials in the entorhinal cortex (EC) was investigated in paralysed and locally anesthetized rats injected with physostigmine in order to induce rhythm. Electrode penetrations through the medial, intermediate and lateral subdivisions of the EC showed in all cases: 1. the presence of rhythm from layer VI to layer III approximately in phase with CA1 rhythm; 2. an amplitude minimum between the outer third of layer III and the inner half of layer I; and 3. a phase-reversed rhythm in layers II-I with an amplitude maximum in the outer half of layer I. Results indicate the existence of neuronal sources of rhythm in the EC.  相似文献   

18.
This study has examined the accumulation of cyclic AMP in microvessels from rabbit and feline cerebral cortex induced by a series of adenosine analogues to determine the type of receptor involved. The conversion of tritium labelled adenine nucleotides to [3H]cyclic AMP was determined in [3H]adenine labelled microvessels in the presence of an inhibitor of cyclic AMP hydrolysis, rolipram (30 microM). In microvessels from both cats and rabbits two adenosine analogues, N-5'-ethylcarboxamido adenosine (NECA) and L (S)-phenylisopropyladenosine (PIA), stimulated cyclic AMP accumulation. The response was larger and more reproducible in rabbits than in cats. In rabbit cerebral microvessels the order of potency as stimulator of cyclic AMP accumulation was NECA greater than 2-chloroadenosine greater than L-PIA greater than cyclohexyladenosine (CHA) greater than D-PIA. This order of potency defines the receptor involved as being of the A2 subtype. Although the maximal response to CHA appeared to be lower than that to NECA, CHA did not inhibit the response to NECA, suggesting that it is not a classical partial agonist. In the presence of the adenylate cyclase stimulating compound forskolin (I microM) NECA was more active than in its absence (close to 30-fold increase in EC50) and also produced a maximal effect six times higher. The maximal responses to PIA and CHA increased proportionally in the presence of forskolin. These results show that rabbit cerebral microvessels possess adenosine receptors of the A2 subtype capable of stimulating the formation of cyclic AMP. The functional significance of such receptors is not known, but may be related to regulation of vascular permeability.  相似文献   

19.
Adenosine activates adenylate cyclase and phospholipase C in mast cells and potentiates stimulated mediator release. To determine whether activation of adenylate cyclase is necessary for the effects of adenosine on the mast cell secretory process, a specific inhibitor of cAMP-dependent protein kinase, KT5720, was used. Antigen and adenosine each induced a rapid increase in mast cell cAMP-dependent protein kinase activity within 30 s. Preincubation with KT5720 (100 nM–10 M) suppressed cAMP-dependent protein kinase activity and inhibited antigen-stimulated -hexosaminidase and leukotriene C4 releases. Adenosine retained its ability to potentiate -hexosaminidase release in antigen- and A23187-stimulated cells even in the presence of complete cAMP-dependent protein kinase inhibition. Mast cells rendered unresponsive to adenosine-related signals by preincubation with adenosine analogs maintained this hyporesponsiveness after incubation with KT5720. It appears that the abilities of adenosine to augment mast cell degranulation and induced receptor hyporesponsiveness are independent of changes in cAMP.  相似文献   

20.
Summary In this paper, we report on our study of frontal midline theta (Fm) activity in human subjects, recorded during mental processes such as arithmetic calculation. The Fm is a 6–7 Hz rhythmic wave with a duration of few seconds. The Fm activity is observed in the central region at the front of the head. EEGs and MEGs of Fm were measured simultaneously during mental calculation, and we analyzed these waveforms based on both topographic EEG maps and magnetic fields measurements. A single dipole simulated the EEG topography adequately, but there are many other dipole models which can generate a similar EEG pattern. It is difficult to estimate the source location of the Fm from the EEG topography alone because the EEG technique has a certain ambiguity associated with source estimation. Therefore, we considered the spatial relationships between the sources and the patterns of EEG and MEG that were simulated. Although it is not possible to obtain a unique solution for the source location of Fm from the EEG data alone, the simultaneous recording of MEGs from a large scalp area may result in an unambiguous solution. We therefore conclude that the simultaneous recording of both MEG and EEG data is more useful for accurate localization, than the EEG alone.  相似文献   

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