Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pyramidal Cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1995

Cortical Lewy body-containing neurons are pyramidal cells: laser confocal imaging of double-immunolabeled sections with anti-ubiquitin and SMI32.

To characterize neurons containing cortical Lewy bodies (LBs), vibratome sections of the superior temporal cortex from eight patients with the LB variant of Alzheimer's disease (LBV) were double-immunolabeled with anti-ubiquitin (a marker of LBs) and anti-nonphosphorylated neurofilament (SMI32; a marker of pyramidal cells) or parvalbumin (PV; a marker of interneurons) and were viewed with a laser-scanning confocal microscope. Almost all (96.1%) the LB-containing neurons were positive for SMI32, but not for PV. Furthermore, the average numbers of SMI32-immunoreactive neurons in layers 3 and 5 were 63% and 77% of those in controls, respectively. PV-immunoreactive neurons showed a greater than 40% decrease. These findings indicate that cortical LB-containing neurons are pyramidal cells and suggest that in LBV, there may be some differences in the degenerative processes effecting pyramidal cells and interneurons.

Aged↗
PubMed1980

On the structure of IIIab-pyramidal cells in the human isocortex. A Golgi and electron microscopical study with special emphasis on the proximal axon segment.

In Golgi preparations of the adult human frontal cortex the IIIab-pyramidal cells show an apical dendrite with numerous side branches and several bifurcating basal dendrites. The dendrites are covered with numerous stalked spines. The axon takes a descending course giving rise to several collaterals. Ultrastructurally the proximal axon segment, i.e. the axon hillock and the initial segment, corresponds in a large degree to descriptions given for that of animals, including the tripartite substructure of the dense undercoating of the axolemma. In the human IIIab-pyramidal cells along the proximal part of the initial segment the undercoating displays gaps not only at the known sites but also opposite astroglial processes. The IIIab-pyramidal cells of the human isocortex require particular interest because they show almost exclusively a recently reported, age-related alteration of their proximal axon segment.

Adult↗
PubMed1992

Enhanced calcium uptake by CA1 pyramidal cell dendrites in the postischemic phase despite subnormal evoked field potentials: excitatory amino acid receptor dependency and relationship to neuronal damage.

After 6-12 h of recovery from transient cerebral ischemia, the pyramidal cells of the hippocampal CA1 region take up excessive amounts of calcium upon electrical stimulation, which has been suggested to be important for the development of delayed neuronal death. The aim of this study was to further characterize this enhanced calcium uptake with respect to time-course of development, relationship to neuronal damage, and amplitude of evoked field potentials as well as the dependency on N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Adult Wistar rats were used and calcium-sensitive microelectrodes were placed in the stratum radiatum of the CA1 hippocampus for recording of the extracellular calcium concentration ([Ca2+]ec) during 20 min of ischemia and for 6 h of reflow. High-frequency stimulation of the perforant pathway elicited burst firing in CA1 and a transient decrease in [Ca2+]ec which reflects neuronal uptake. Shifts in [Ca2+]ec could not be evoked 0-1 h after ischemia. However, from 1-2 h burst firing could be evoked and the accompanying shift in [Ca2+]ec increased thereafter in amplitude with prolonged reflow, exceeded preischemic levels after 4 h, and reached 250 +/- 116% (mean +/- SD) of control after 6 h of reflow (p less than 0.05). The extracellular reference potential shift during electrical stimulation and the amplitude of evoked field potentials were still subnormal after 6 h [85 +/- 25% and 83 +/- 25%, respectively (mean +/- SD)]. There was a significant correlation between the degree of stimulated calcium uptake at 6 h postischemia and the extent of CA1 damage evaluated 7 days after the ischemic insult (r = 0.849; p less than 0.001). The shifts in [Ca2+]ec were reduced by the NMDA antagonist MK-801 (0.5-2 mg/kg, i.v.) to approximately 50% of the initial level during both control and postischemic conditions (p less than 0.01). The non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[F]quinoxaline (NBQX) (42 +/- 13 mg/kg, i.p.; mean +/- SD) decreased the amplitude of the evoked field potentials (to 30 +/- 28% of control, p less than 0.05) and completely abolished the evoked shifts in [Ca2+]ec. In conclusion, the uptake of calcium into CA1 pyramidal cells during electrical stimulation was enhanced already 4 h after ischemia in spite of the fact that other measures of excitability were subnormal. This calcium uptake correlated to the extent of CA1 pyramidal cell damage and was dependent on both NMDA and non-NMDA receptor activation.

Analysis of Variance↗
PubMed1992

Neuropathology of the chronic epileptic syndrome induced by intrahippocampal tetanus toxin in rat: preservation of pyramidal cells and incidence of dark cells.

A few nanograms of tetanus toxin injected into a rat hippocampus causes a chronic epileptic syndrome characterized by brief seizures that recur intermittently for about 6 weeks. Cognitive and other behavioural impairments persist after the seizures and other epileptic electrographic activity have remitted, and may be permanent. Our previous studies suggested that the behavioural changes following seizure remission were an indication of functional impairment associated with decreased neuronal excitability rather than with neuronal loss. The conclusion that neurons were preserved relied on qualitative histological observations and, indirectly, on electrophysiological measurements of the amplitudes of antidromic population spikes. Recently, gross histopathology has been described in a quantitative histological study of rats 7-10 days after they had received rather higher doses of intrahippocampal tetanus toxin. Here we report a quantitative histological study of hippocampi from rats which had gained remission from seizures induced by low doses of tetanus toxin. Adult Sprague Dawley rats received unilateral injections of 3-4 ng (about 6-8 mouse LD50) tetanus toxin, or vehicle, into the dorsal hippocampus. The first experiment confirmed that postsynaptic evoked responses recorded from pyramidal cells were depressed 10-19 weeks after injection. Unexpectedly, there also was a decrease of 20% in the antidromic response from CA3a contralateral to the injection. However, cell counts in these hippocampi revealed no change in pyramidal cell numbers. The second experiment used rats from two breeding colonies, prepared for histology 7 weeks after injection. Hippocampal pyramidal cell numbers were within the normal range in all but three of the 24 rats that had received tetanus toxin. These three had lesions of the CA1 pyramidal layer contralateral to the injection. The lesions were of the order of 2 mm in diameter, and were associated with glial proliferation. When these three cases were excluded, there remained a small increase in glial density in CA1 of the toxin-injected rats. In addition, toxin-injected rats from one of the colonies were susceptible to a pathology known as acidophylic or dark cell change. These occurred in 11 of 18 toxin-injected rats from this colony, in all divisions of the pyramidal layer, in both the injected and the contralateral hippocampus (where parallel studies revealed independent secondary epileptic foci). We conclude that loss of pyramidal neurons is not necessary for the persistent behavioural changes in this model.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

[Relation between lipofuscin content and organelle density in pyramidal cells of laminae III and V of area 10 (Brodmann) of the cerebral frontal lobe of humans of different ages].

The areal portion of the lipofuscin granules and mitochondria contained in ultrathin sections, the length of rough endoplasmic reticulum (RER) and the numerical density of ribosomes were determined in the pyramidal cells of layers III and V of area 10 (Brodmann) of the frontal brains of six newly died persons of different ages. This revealed considerable differences in lipofuscin contents and numerical density of organelles between the pyramidal cells and greater values, on an average, for the pyramidal cells of layer III. The comparison of averages for the single brains did not show the continuity nor the age dependence of changes but rather the individual variability of these processes. The expected decrease of the density of organelles with increasing lipofuscin contents was found more frequently only at extremely high values of lipofuscin contents. It becomes evident that even under the conditions of lipofuscin accumulation the permanently necessary physiological renewal of cell structures involved in metabolism is guaranteed over a longer period of time and that their full performance is almost completely unimpaired during this phase.

Adult↗
PubMedDate not supplied

The action of thallium on the excitability of CA1 pyramidal cells in hippocampal slices.

The effect of thallium ions on central neuronal activity was investigated in hippocampal slice preparations from guinea pigs and rats using extra- and intracellular recording techniques. Thallium induced a reversible and concentration-dependent reduction of the orthodromically evoked compound action potential of CA1 pyramidal cells with only weak effects on either afferent fiber activity, postsynaptic potentials or antidromically evoked responses. The membrane potential and input resistance of the pyramidal cells were not impaired by thallium. In contrast, variations in the maintained spike activity and spontaneously occurring inhibitory postsynaptic potentials were observed. It is concluded, that in contrast to its presynaptic action in the peripheral nervous system, thallium has a predominant postsynaptic target site in the hippocampal slice preparation. It is suggested that the neurotoxic action of thallium is not mediated by an interaction with specific ion channels of the cell membrane, but rather by an unspecific influence on the intracellular metabolism of the CA1 pyramidal cell.

Action Potentials↗
PubMed1990

Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat.

The distribution of intrahippocampal projections arising from the CA3 region of the rat hippocampus was investigated using in vitro and in vivo methods. In the in vitro hippocampal slice preparation, single CA3 pyramidal cells were intracellularly labeled with horseradish peroxidase (HRP), and the three-dimensional organization of the axonal plexus was analyzed by using a computer-aided digitizing system. As many as eight primary collaterals originated from the principal axon of CA3 pyramidal cells and these commonly bifurcated further and innervated stratum oriens and stratum radiatum of CA3 and CA1. Within the 400 microns slice, the summed length of all visible collaterals per neuron ranged from 2.6 mm to approximately 12.5 mm. While the CA3 principal axon tended to be relatively smooth, the axonal collaterals bore numerous varicosities that electron microscopy confirmed to be presynaptic boutons. These varicosities occurred, on average, once every 7 microns of collateral length. The distribution of axonal collaterals differed depending on the location of the parent pyramidal cell. Only rarely could CA3 collaterals be followed in the slice to their terminations within CA1. To study the topographic organization of CA3 projections both to other levels of CA3 and to CA1, the anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into various transverse and septotemporal levels of CA3. Immunohistochemical visualization of the lectin was conducted in dissected and "extended" hippocampi to facilitate analysis of the topographic distribution of projections along the long or septotemporal axis. Projections from all portions of CA3 reached widespread regions of CA3, CA2, and CA1, but only a few fibers entered the subicular complex and there were no projections to the entorhinal cortex. There were also some CA3 and CA2 projections to the hilus of the dentate gyrus, but these did not enter the granule cell or molecular layers. The CA3 projections to CA1 were organized according to several distinctive and consistent gradients that can generally be summarized as follows. 1. CA3 cells located close to the dentate gyrus (proximal CA3), while projecting both septally and temporally, tended to project more heavily to levels of CA1 located septal to the injection site. CA3 cells located closer to CA1, in contrast, projected more heavily to levels of CA1 located temporally to the injection site. 2. At, or close to, the septotemporal level of the injection, cells located proximally in CA3 gave rise to collaterals that tended to terminate more superficially in stratum radiatum than did those arising from mid and distal levels of CA3.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Baclofen selectively inhibits transmission at synapses made by axons of CA3 pyramidal cells in the hippocampal slice.

The effects of baclofen, an antispastic drug, on excitatory transmission were tested by bath application to the hippocampal slice preparation. (+/-)-Baclofen (20 microM) strongly depressed extracellularly recorded synaptic responses to stimulation of projections that originate from CA3 hippocampal pyramidal cells. Responses to stimulation of four other excitatory pathways were little affected and the amplitudes of presynaptic fiber potentials and antidromic responses were unaltered. When tested on the Schaffer collateral-commissural-CA1 pyramidal cell synapse. (-)-baclofen depressed the amplitude of the extracellular excitatory postsynaptic potential with an IC50 of 3.7 microM and was 180 times more potent than (+)-baclofen. gamma-Aminobutyric acid, 3-aminopropanesulfonic acid and imidazole-4-acetic acid also inhibited transmission at this site. Baclofen could suppress the response completely, and its action was unaffected by bicuculline. In contrast, imidazole-4-acetic acid could suppress the response by a maximum of only 75%, and its action was highly sensitive to bicuculline. gamma-Aminobutyric acid and 3-aminopropanesulfonic acid could suppress the response completely, and their actions were relatively weakly antagonized by bicuculline. These results are consistent with the hypothesis that baclofen inhibits excitatory transmission by interacting with a bicuculline-insensitive gamma-aminobutyric acid receptor. These receptors may be located on one type of glutamatergic/aspartergic synaptic terminal, exemplified by axon terminals of CA3 hippocampal pyramidal cells. Synapses made by these axons may therefore serve as models for studying the mechanism of action of baclofen.

Action Potentials↗
PubMed1986

Effects of histamine on hippocampal pyramidal cells of the rat in vitro.

The actions of bath applied histamine on CA1 pyramidal cells were investigated in hippocampal slices of the rat. Histamine caused a) a slight depolarization but no significant change in resting membrane conductance; b) an abbreviation of long afterhyperpolarizations after single action potentials, bursts of action potentials or TTX resistant spikes; c) a loss of accommodation of firing. In the presence of TEA or barium, histamine prolonged and increased the size and number of the slow TTX resistant spikes. A depolarizing plateau which follows such spikes was also increased by histamine, but the population spike was increased. The frequency of spontaneous chloride dependent potentials, which reflect interneurone firing, was also increased. These effects considerably outlasted histamine application and were mimicked by the H2-agonist impromidine but not the H1-agonist thiazolethylamine, and blocked by the H2-antagonists cimetidine and metiamide but not the H1-antagonists mepyramine or the beta-antagonist propranolol. It is concluded that histamine, by activating H2-receptors, antagonizes a calcium mediated potassium conductance in hippocampal pyramidal cells without affecting calcium current. By this mechanism histaminergic afferent fibres could effectively regulate cortical responsiveness by selectively potentiating large excitatory inputs of target neurones.

Animals↗
PubMed1994

5-HT1A receptor linked to inward-rectifying potassium current in hippocampal CA3 pyramidal cells.

1. Voltage- and current-clamp intracellular recordings were performed on rat CA3 hippocampal pyramidal cells in a slice preparation. 2. Under current-clamp conditions, 5-hydroxytryptamine (5-HT) or baclofen (BAC) perfusion hyperpolarized CA3 cells. 3. Under single-electrode voltage-clamp conditions, 5-HT perfusion elicited an outward current flow that was blocked by 2 mM BaCl2 but not by 100 microM CdCl2. 4. The Emax of the current response in CA3 was larger than that elicited in CA1 and the potency was less in CA3 than CA1. 5. Increasing the external potassium concentration shifted the reversal potential for the 5-HT-mediated response. 6. The potassium current exhibited inward rectification. 7. The BAC- and 5-HT-mediated currents were not additive. 8. Pertussis-toxin (PTX) treatment blocked both 5-HT- and BAC-elicited hyperpolarizations. 9. On the basis of these results, we conclude that 5-HT hyperpolarized hippocampal CA3 pyramidal cells by increasing an inward-rectifying potassium conductance. Furthermore both the 5-HT1A and gamma-aminobutyric acidB (GABAB) receptors are linked to potassium channels via a PTX-sensitive G protein.

Animals↗
PubMed1988

Water-maze learning and effects of cholinergic drugs in mouse strains with high and low hippocampal pyramidal cell counts.

Morphological differences have been found in inbred strains of mice in the number and volume of pyramidal cells in Ammon's horn of the hippocampus. Among the mouse strains surveyed, NZB/BINJ (NZB) and C57BL/10J (B10) are most divergent in both total volume and total number of neurons. These genetically derived differences were exploited to determine hippocampal involvement in the acquisition of a spatial water maze. Genetic differences in hippocampal cell number were related to the acquisition of this spatial task. Mice with small numbers of hippocampal pyramidal cells, the B10 strain, acquired a water-maze task more slowly than either NZB mice or (NZBxNZW) F1 (NZBWF) animals. In addition, strain differences in responsivity to cholinergic manipulations were found. B10 mice were more sensitive than NZB or NZBWF mice to both the disruptive effects of scopolamine and the facilitory effects of physostigmine on swim maze learning. Although other inherited differences undoubtedly exist between these strains as is apparent in other mouse lines, these data suggest a prominent role for the hippocampus in the learning of spatially oriented behavior. Furthermore, this behavior appears to be responsive to cholinergic manipulations.

Animals↗
PubMed1994

Synapses on axon collaterals of pyramidal cells are spaced at random intervals: a Golgi study in the mouse cerebral cortex.

In this study we investigated the arrangement of synapses on local axon collaterals of Golgi-stained pyramidal neurons in the mouse cerebral cortex. As synaptic markers we considered axonal swellings visible at high magnification under the light microscope. Such axonal swellings coincide with synaptic boutons, as has been demonstrated in a number of combined light and electron microscopic studies. These studies also indicated that, in most cases, one bouton corresponds precisely to one synapse. Golgi-impregnated axonal trees of 20 neocortical pyramidal neurons were drawn with a camera lucida. Axonal swellings were marked on the drawings. Most swellings were 'en passant'; occasionally, they were situated at the tip of short, spine-like processes. On axon collaterals, the average interval between swellings was 4.5 microns. On the axonal main stem, the swellings were always less densely packed than on the collaterals. Statistical analysis of the spatial distribution of the swellings did not reveal any special patterns. Instead, the arrangement of swellings on individual collaterals follows a Poisson distribution. Moreover, the same holds to a large extent for the entire collection of pyramidal cell collaterals. This suggests that a single Poisson process, characterized by only one rate parameter (number of synapses per unit length), describes most of the spatial distribution of synapses along pyramidal cell collaterals. These findings do not speak in favour of a pronounced target specificity of pyramidal neurons at the synaptic level. Instead, our results support a probabilistic model of cortical connectivity.

Animals↗
PubMed1987

Phorbol esters broaden the action potential in CA1 hippocampal pyramidal cells.

Intracellular recordings were made from CA1 pyramidal cells in rat hippocampal slices. Single action potentials were elicited by injection of brief current pulses. Bath application of phorbol esters (4 beta-phorbol-12,13-diacetate, 0.3-5 microM; or 4 beta-phorbol-12,13-dibutyrate, 5-10 microM) broadened the action potential in each of the cells tested (n = 9). The broadening reflected slowing of the repolarization, whereas the upstroke of the spike was unchanged. This effect may enhance transmitter release from synaptic terminals, and contribute to enhancement of synaptic transmission through activation of protein kinase C, a mechanism which has been associated with long term potentiation.

Action Potentials↗
PubMed1986

Facilitating and nonfacilitating synapses on pyramidal cells: a correlation between physiology and morphology.

Pyramidal cells in piriform cortex receive excitatory inputs from two different sources that are segregated onto adjacent segments of their apical dendrites. The present studies show that excitatory postsynaptic potentials (EPSPs) evoked by primary olfactory tract afferents that terminate on distal apical segments display paired shock facilitation whereas ESPSs evoked by intrinsic association fibers that terminate on proximal apical segments do not. An ultrastructural comparison of the presynaptic elements of these two fiber systems has revealed that the facilitating olfactory tract afferent synapses have a much lower packing density of synaptic vesicles than do the nonfacilitating association fiber synapses. Further, a search of the literature has revealed that where both morphological and physiological data are available for the same synapses, this same correlation appears to apply. We propose a hypothesis to account for this correlation based on synaptic vesicles to buffer internal calcium and the biochemical characteristics of preterminal calcium-dependent mechanisms affecting the number of vesicles available for release.

Animals↗
PubMed1978

Identification of pyramidal cells as the critical elements in hippocampal neuronal plasticity during learning.

The activity of single neurons recorded from rabbit hippocampus during classical conditioning of the nictitating membrane reflex was studied. All cells were first categorized according to their responses after fornix stimulation--i.i., antidromic activation, orthodromic activation, or no activation. The majority of cells that were antidromically activated--pyramidal cells--showed a highly positive correlation between the pattern of unit discharge and the topography of the nicititating membrane response within trial periods. Units that were orthodromically driven by fornix stimulation tended to inhibit during the presentation of trial stimuli, whereas most non-activated cells maintained low spontaneous levels of activity at all times. Thus, the major output neurons of the hippocampus appear to be the neuroanatomical substrate for the large and rapidly developing neuronal plasticity induced by this classical conditioning paradigm.

Action Potentials↗
PubMed1980

Age-related alterations of the proximal axon segment in lamina IIIab-pyramidal cells of the human isocortex. A Golgi and fine structural study.

In the human isocortex preferably the pyramidal cells of layer IIIab are subjected to a conspicuous age-related alteration in that they develop spindle-shaped enlargements of their proximal axon segment. In Golgi impregnations such IIIab-pyramidal cells with an axon dilatation do not display obvious alterations in the ramification or spine density of their dendrites. Electron microscopically different degrees of this alteration can be recognized; beginning with a cone-shaped and slight dilatation and culminating in a giant spindle-shaped enlargement of the proximal axon segment. The fasciculated microtubules normally characterizing the initial segment are pushed aside or are lacking. Lipofuscin granules, RER cisterns and ribosome rosettes penetrate into the dilatation. The axolemma of those parts of the axon segment in the vicinity of which lipofuscin granules can be encountered lacks a dense axolemmal undercoating. As concerns the adjacent profiles of the dilatation there are no obvious alterations in comparison to a normal proximal axon segment. A slender process arises distally from the dilatation showing the morphological characteristics of the axon initial segment.

Aged↗
PubMed1994

Amplification and linearization of distal synaptic input to cortical pyramidal cells.

1. Computer simulations were used to study the effect of voltage-dependent calcium and potassium conductances in the apical dendritic tree of a pyramidal cell on the synaptic efficacy of apical synaptic input. The apical tuft in layers 1 and 2 is the target of feedback projections from other cortical areas. 2. The current, Isoma, flowing into the soma in response to synaptic input was used to assess synaptic efficacy. This measure takes full account of all the relevant nonlinearities in the dendrities and can be used during spiking activity. Isoma emphasizes current flowing in response to synaptic input rather than synaptically induced voltage change. This measure also permits explicit characterization of the input-output relationship of the entire neuron by computing the relationship between presynaptic input and postsynaptic output frequency. 3. Simulations were based on two models. The first was a biophysically detailed 400-compartment model of a morphologically characterized layer 5 pyramidal cell from striate cortex of an adult cat. In this model eight voltage-dependent conductances were incorporated into the somatic membrane to provide the observed firing behavior of a regular spiking cell. The second model was a highly simplified three-compartment equivalent electrical circuit. 4. If the dendritic tree is entirely passive, excitatory synaptic input of the non-N-methyl-D-aspartate (non-NMDA) type to layers 1, 2, and 3 saturate at very moderate input rates, because of the high input impedance of the apical tuft. Layers 1 and 2 together can deliver only 0.25 nA current to the soma. This modest effect is surprising in view of the important afferents that synapse on the apical tuft and is inconsistent with experimental data indicating a more powerful effect. 5. We introduced in a controlled manner a voltage-dependent potassium conductance in the apical tuft, gK, to prevent saturation of the synaptic response. This conductance was designed to linearize the relationship between presynaptic input frequency and the somatic current. We also introduced a voltage-dependent calcium conductance along the apical trunk, gCa, to amplify the apical signal, i.e., the synaptic current reaching the soma. 6. To arrive at a specific relationship between the presynaptic input rate and the somatic current delivered by the synaptic input, we derived the activation curves of gK and gCa either analytically or numerically. The resultant voltage-dependent behavior of both conductances was similar to experimentally measured activation curves.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Kappa 2 opioid receptors inhibit NMDA receptor-mediated synaptic currents in guinea pig CA3 pyramidal cells.

The role of the endogenous opioid peptide dynorphin (1-17) in regulating NMDA receptor-mediated synaptic currents was examined in guinea pig hippocampus. Schaffer collateral/commissural fiber-evoked NMDA synaptic currents were recorded using whole-cell patch-clamp techniques in CA3 pyramidal cells. Dynorphin was found to have dual effects on NMDA synaptic currents, increasing currents at low concentrations and decreasing currents at high concentrations. Only the inhibitory action of dynorphin was sensitive to naloxone, indicating that this effect was mediated by an opioid receptor. The inhibitory effect was mimicked by bremazocine, but not by U69,593, U50,488, [D-Ala2, N-Me-Phe4, Gly-ol]-enkephalin, or [D-Pen2,5]-enkephalin. Bremazocine's effect was blocked by naloxone, but not by nor-binaltorphimine, cyprodime, or naltrindole. These findings suggest that bremazocine's effect was mediated by the kappa 2 subtype of opioid receptor. In addition, 1 microM naloxone and antisera to dynorphin (1-17) were found to increase NMDA-mediated synaptic currents. Nor-binaltorphimine, cyprodime, naltrindole, and antisera to met-enkephalin did not increase the NMDA synaptic current. These findings suggest that endogenous dynorphin was acting at kappa 2 receptors to inhibit NMDA receptor-mediated synaptic currents. Overall, these findings indicate that dynorphin is an endogenous agonist for kappa 2 receptors in the CA3 region of the guinea pig hippocampus and that these receptors regulate NMDA receptor function.

Animals↗