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P Schubert

Publications and source records attributed to P Schubert.

At least 73 records · Page 4Linked to original sources
PubMed1986

Non-synaptic modulation of repetitive firing by adenosine is antagonized by 4-aminopyridine in a rat hippocampal slice.

In rat hippocampal slices which were superfused with low calcium (0.2 mM) medium, stimulation of the alvear fibers elicited an extracellularly recorded antidromic population spike in CA1 pyramidal neurons which was followed by 2-4 afterpotentials. Adenosine (20-40 microM) and the A1-adenosine agonist 1-phenylisopropyladenosine (L-PIA) blocked these afterpotentials without affecting the first spike. Addition of up to 5 mM tetraethylammonium to the superfused medium did not interfere with this adenosine action. But the addition of only 50 microM 4-aminopyridine (4-AP) antagonized almost completely the adenosine- or L-PIA-induced depression of antidromically evoked repetitive firing. It is concluded that functioning of 4-AP-sensitive potassium channels is a prerequisite for this 'antiepileptic' adenosine action. Since a similar pharmacological characteristic has been described for the A-current, it is likely that adenosine acts by turning on this particular potassium current.

4-Aminopyridine↗
PubMed1986

Differential effect of adenosine on pre- and postsynaptic calcium fluxes.

In rat hippocampal slices, stimulus-evoked field potentials and the concomitant decrease of the extracellular concentration of free Ca ions [Ca2+]o were measured with combined reference/ion-sensitive microelectrodes. By reducing [Ca2+]o from 2.0 mM to 0.2 mM, evoked synaptic transmission was blocked, but orthodromic repetitive stimulation of CA1 afferents still elicited a marked decrease of [Ca2+]o. This Ca2+ signal is attributed predominantly to Ca2+ entry into the activated axon terminals. It was significantly depressed by adenosine. The adenosine agonist, L-phenylisopropyl adenosine (L-PIA) was more effective than D-PIA, indicating that the adenosine depression of presynaptic Ca2+ entry is mediated via the A1 receptor. 4-Aminopyridine (4-AP) enhanced decreases in [Ca2+]o without restoring synaptic transmission. Adenosine depressed also these Ca2+ signals. Adenosine deaminase was even more effective in the presence of 4-AP and enhanced the orthodromic Ca2+-signal by a factor of two. Antidromic stimulation of hippocampal pyramidal cells also evoked reductions in [Ca2+]o. These were less affected by adenosine and the other treatments under the conditions tested.

Adenosine↗
PubMed1986

The distribution of adenosine A1 receptors and 5'-nucleotidase in the hippocampal formation of several mammalian species.

The distributions of adenosine A1 receptors, as demonstrated by 3H-cyclohexyladenosine (3H-CHA) binding, and the adenosine-producing enzyme 5'-nucleotidase were examined in the hippocampal formation of the rat, mouse, gerbil, cat, hamster, rabbit, and guinea pig. The enzyme and binding sites were restricted to subregions and often individual layers of this structure. The distribution of 3H-CHA binding was consistent among the species with the strata radiatum and oriens of fields CA1 and CA3 exhibiting the highest levels of binding. A distinct band of 3H-CHA binding was observed in the stratum moleculare of the dentate gyrus; and in most species, this band was restricted to the inner one-third of the stratum moleculare (i.e., proximal to the stratum granulosum). The strata pyramidale, granulosum, and lucidum were in general only weakly positive for 3H-CHA binding. The binding to the stratum lacunosum/moleculare (or the distinct strata lacunosum and moleculare in the rabbit and cat) was moderate. In contrast to the relative consistency of the patterns of 3H-CHA binding in these species, 5'-nucleotidase exhibited wide variations in both the absolute amount of activity and its localization. In all species, the strata granulosum and pyramidale appeared devoid of 5'-nucleotidase activity. The only clear exception to this rule was the CA3 region of the cat where activity was seen between the cell bodies of stratum pyramidale. The strata radiatum and oriens of CA1 were strongly positive in the rat and hamster but only low to moderately stained in the other species examined.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗
PubMed1984

The anticonvulsive action of adenosine: a postsynaptic, dendritic action by a possible endogenous anticonvulsant.

Neural afterdischarges generated in the presence of penicillin or low extracellular calcium concentrations were found to be inhibited by adenosine in the rat hippocampus in vitro. This anticonvulsant effect of adenosine is observed in the absence, as well as in the presence, of chemical synaptic transmission and apparently occurs at a postsynaptic site which is most sensitive in the apical dendritic region of the CA1 pyramidal cells. The methylxanthine theophylline antagonizes the effect of adenosine; and, the anticonvulsant action of the L-isomer of the adenosine analogue phenylisopropyladenosine (PIA) is substantially more potent than the D-isomer, findings which are characteristic of an A1 type adenosine receptor. The endogenous release of adenosine may therefore serve to tonically reduce the tendency for repetitive discharge in CA1 pyramidal cells via an interaction with a high affinity A1 receptor which appears to be preferentially localized in the apical dendrites.

Adenosine↗
PubMed1983

Adenosine receptor density and the depression of evoked neuronal activity in the rat hippocampus in vitro.

The relationship between the heterogeneous distribution of A-1 adenosine receptors and the capacity of adenosine to depress neuronal activity was examined in the rat hippocampus. Utilizing autoradiographic techniques, the distribution of A-1 adenosine receptors was assessed by the binding of [3H]cyclohexyladenosine ([3H]CHA) to cryostat sections of rat brain. The apical dendritic region of CA1 showed a differential distribution of adenosine receptors between the stratum radiatum and stratum lacunosum/moleculare. The physiological relevance of this binding difference was studied in the hippocampal slice by examining the capacity of adenosine to depress evoked potentials in these two strata. It was observed that the receptor differences correlated with differential sensitivities to adenosine modulation of the evoked potentials. These data suggest that receptor density, as shown by binding techniques, may provide not only a qualitative but also a quantitative map of the sites of adenosine action.

Adenosine↗
PubMed1983

Regulation of the strength of adenosine modulation in the hippocampus by a differential distribution of the density of A1 receptors.

Correlative studies examining: (1) the binding of [3H]cyclohexyladenosine to A1 adenosine receptor sites, and (2) the depressive action of adenosine on evoked activity, were performed in the hippocampal formation. A greater number of A1 sites was observed in the dorsal versus ventral aspect of the hippocampus, and a larger depression of evoked potentials by adenosine was obtained in the dorsal aspect. These observations suggest that a differential density of A1 receptors might control the magnitude of modulatory action by adenosine on hippocampal circuitry.

Adenosine↗
PubMed1982

An A1-adenosine receptor, characterized by [3H] cyclohexyladenosine binding, mediates the depression of evoked potentials in a rat hippocampal slice preparation.

In slices of rat hippocampus, adenosine and several adenosine derivatives depressed evoked neuronal responses to afferent stimulation. The nanomolar potency of adenosine derivatives and their relative effectiveness indicate that the depression of evoked potentials is mediated via an A1-adenosine receptor. A remarkable similarity was found between the relative potencies of nucleoside derivatives with respect to their electrophysiological effects and to their inhibition of high affinity [3H] cyclohexyladenosine ([3H]CHA) binding to rat brain membranes. We conclude that the [3H] CHA binding site in rat brain membranes represents a physiological receptor of the A1-type.

2-Chloroadenosine↗
PubMed1982

A combined in vivo/in vitro study of the presynaptic release of adenosine derivatives in the hippocampus.

To investigate the release of adenine compounds from defined neuronal pathways, we employed a hippocampal slice preparation in which a selective-loading of the releasable pools was achieved in vivo with the aid of axonal transport. By injecting radioactive adenosine stereotaxically into the entorhinal cortex, the major afferent system to the dentate gyrus (the perforant path) was loaded within 20-36 h, at which time the rats were killed and hippocampal slices were prepared. The efflux of radioactive material, as recovered from the perfusate and measured in a scintillation counter, was found to be significantly increased in response to electrophysiologically controlled stimulation of the perforant path but not to stimulation of an alternative fiber tract, the fimbria. These findings provide supportive and more direct evidence for an activation-coupled release of adenosine derivatives from presynaptic sites in the central nervous system.

Adenosine↗
PubMed1981

Effect of adenosine versus adenine nucleotides on evoked potentials in a rat hippocampal slice preparation.

A marked depression of evoked CA1 potentials was observed with the nucleotide analogues a,b-methylene ADP (AOPCP) and adenylimido-diphosphate (AIP) and with 2'-adenosine monophosphate (2'-AMP). While the depression elicited by 5'-nucleotides was completely antagonized by the action of adenosine deaminase, AOPCP and 2'-AMP were only partially antagonized. The findings indicate that nucleotides on their own are capable of modulating synaptic transmission but that the physiologically more prevalent 5'-AMP is mediating its effect via adenosine. By producing this membrane permeable compound and allowing its re-uptake, the 5'-nucleotidase may determine the time course of purinergic action.

Adenine Nucleotides↗
PubMed1981

Adenosine depression of hippocampal neurons in vitro: an intracellular study of dose-dependent actions on synaptic and membrane potentials.

In CA1 pyramidal neurons, 5 micrometer adenosine had no measurable effect on resting membrane potential or resistance, while excitatory and inhibitory postsynaptic potentials generated by orthodromic stimulation of the stratum radiatum were reduced by 20--60%. However, 10--20 micrometers adenosine not only markedly reduced (by 20--80%) the synaptic potentials, but also clearly hyperpolarized most pyramidal neurons. This effect was accompanied by a reduction in input resistance in about one-half of the cells and no measurable change in resistance in the rest. Monobutyryl cyclic AMP in concentrations of 50 micrometer or more also hyperpolarized neurons, usually no change in input resistance.

Adenosine↗
PubMed1981

Selective localization of different types of opiate receptors in hippocampus as revealed by in vitro autoradiography.

The visualization of opiate binding sites within the hippocampus of the rat has been achieved by means of an in vitro autoradiography. In line with the concept of multiple opiate receptors, different opioid agonists revealed a particular distribution pattern. Whereas the selective delta-receptor agonist [3H]D-Ala2,D-Leu5-enkephalin specifically labelled binding sites in the CA2 area, [3H]etorphine grains displayed a uniform dense distribution throughout the pyramidal cell layers from CA1 to CA4.

Animals↗
PubMed1981

A selective distribution pattern of different opiate receptors in certain areas of rat brain as revealed by in vitro autoradiography.

A differential localization of binding sites in the rat brain for [3H]D-Ala2,Leu5-enkephalin ([3H]DADL) and [3H]etorphine ([3H]Eto) was been demonstrated by an in vitro autoradiography technique. Labeling with [3H]DADL was found predominantly in septum and paraventricular nuclei of hypothalamus, whereas [3H]Eto labeling was primarily observed in the periaqueductal gray and several thalamic nuclei. The distinctive patterns of labeling by the two ligands in certain central nervous system structures suggests the existence of specific neuronal pathways which are preferentially labeled with either [3H]DADL or [3H]Eto.

Animals↗