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Biomedical subjects

Z Elazar

Publications and source records attributed to Z Elazar.

At least 37 records · Page 2Linked to original sources
PubMed1993

Recordings of the evoked auditory wave P1 from the pons during natural and drug-induced REM.

A positive component of the middle latency auditory evoked response recorded from the vertex, the P1 wave, was found to be sensitive to changes in the wakefulness-sleep states. We report here that this wave can be recorded from the pons of chronically prepared cats. During natural REM sleep and REM induced by micro-injections of carbachol and neostigmine into the pons the pontine P1 had amplitudes much higher than during slow wave sleep (SWS). The increase in amplitude was dose dependent. Scopolamine had a profound and long-lasting weakening effect on the wave. These results indicate a relation between the P1 wave and the cholinergic generator mechanism for REM sleep. Also, our results support the role of an increased recruitment of the pontine neurones in the generation of REM sleep.

Animals↗
PubMed1992

Similarities between the akinesia induced by carbachol microinjections into the pontine reticular formation and neuroleptic catalepsy.

We reported previously that microinjections of carbachol directly into the pontine reticular formation of rats induced intense akinesia. In the present article we report results of tests for rigidity, righting, bracing and clinging which were conducted with the purpose to characterize behaviorally this type of akinesia. After injections of 5-15 micrograms/0.5 microliter of carbachol into the pontine reticular formation the rats were cataleptic, were not rigid when equilibrium was not challenged, had strong righting reflexes and strong bracing and clinging responses. This type of akinesia is different from the catatonia induced by systemic morphine (20 mg/kg IP), but similar to the catalepsy induced by systemic injections of haloperidol (5 mg/kg IP). It is thus suggested that the cataleptic state produced by topical carbachol in the pons is related to the dopaminergic mechanisms important for the cataleptic effect of the neuroleptic drugs.

Analysis of Variance↗
PubMed1991

Vanadate inhibits agonist binding to D2 dopamine receptor.

Orthovanadate (in the micromolar range) inhibits the high-affinity binding of the D2 dopamine receptor to specific agonists (apomorphine and N-propylnorapomorphine), while it does not affect the binding to D2 antagonists (spiperone and haloperidol). These effects of vanadate resemble those observed with guanine nucleotides or their analogs. However, in contrast to the guanine nucleotides, vanadate does not induce dissociation of the D2 dopamine receptor from its related G proteins, suggesting that vanadate and guanine nucleotides may exert their effect on the D2 dopamine receptor via different mechanisms. The effect of vanadate on agonist binding was shown to be ATP dependent and correlated with increased protein phosphorylation.

Animals↗
PubMed1991

Phosphorylation by cyclic AMP-dependent protein kinase modulates agonist binding to the D2 dopamine receptor.

Phosphorylation of striatal membranes by cyclic AMP-dependent protein kinase resulted in a reduction in the affinity of the D2 dopamine receptor toward its agonist N-propylnorapomorphine while the affinity to D2-specific antagonists remained unchanted. The inhibitory effects observed by phosphorylation and guanine nucleotides on agonist binding to the D2 receptor were additive. The purified D2 dopamine receptor from bovine striatum was specifically phosphorylated by cyclic AMP-dependent protein kinase with an apparent stoichiometry of 0.7 mol phosphate/mol receptor. The phosphorylated purified D2 receptor also exhibited a reduced agonist binding activity with no change in antagonist binding. The action of cyclic AMP-dependent protein kinase on both the membrane preparation and the purified D2 receptor was inhibited by a specific inhibitor of the kinase. These data indicate that phosphorylation mediated by cyclic AMP-dependent protein kinase may represent a physiological pathway for modulation of the receptor binding activity.

Animals↗
PubMed1990

Dopaminergic drugs influence the intensity of catalepsy induced by microinjections of carbachol into the reticular formation.

Carbachol microinjections into the mesencephalic and pontine reticular formation in rats induced intense and long-lasting catalepsy. Systemically administered haloperidol potentiated, while apomorphine and L-DOPA reduced the cataleptogenic effect of carbachol. These results indicate the existence of functional relations between the cholinergic cataleptogenic mechanism in the reticular formation and the dopaminergic system. They are interpreted in the light of known anatomical ascending and descending interconnections between the reticular formation and basal ganglia.

Animals↗
PubMed1990

Catalepsy induced by carbachol microinjected into the pontine reticular formation of rats.

Rats were implanted stereotaxically with permanent guide tubes aimed at the pontine reticular formation. Carbachol was microinjected in the awake, freely moving rats. Catalepsy was evaluated with the horizontal bar test. Intense and long-lasting, dose-dependent catalepsy was observed following microinjections of 2-8 micrograms of carbachol. Pretreatment with intraperitoneally administered scopolamine significantly reduced the cataleptogenic effect of carbachol. These results show that the pontine reticular formation is part of the neuroanatomical substrate of catalepsy induced by cholinergic drugs.

Animals↗
PubMed1989

Association of two pertussis toxin-sensitive G-proteins with the D2-dopamine receptor from bovine striatum.

The solubilized D2-dopamine receptor from bovine striatum exhibits high and low affinity states for dopaminergic agonists. Guanine nucleotides and pertussis toxin convert the solubilized receptor from a high affinity state to a low one. A D2-receptor preparation partially purified by affinity chromatography on a haloperidol adsorbent, exhibited agonist-stimulated GTPase activity. [32P]ADP-ribosylation by pertussis toxin of this receptor preparation resulted in the specific labeling of two protein bands corresponding to mol. wts of 39 and 41 kd, in SDS-PAGE. Association of these G-proteins with the receptor was specifically inhibited by Gpp(NH)p. Immunoblot analysis of these G-proteins indicated that the 41- and 39-kd protein bands are analogous to brain Gi and Go respectively. These experiments demonstrate that two distinct pertussis toxin-sensitive G-proteins are functionally associated with bovine striatum D2-dopamine receptor.

Adenosine Diphosphate↗
PubMed1988

Purification of the D-2 dopamine receptor from bovine striatum.

The D-2 dopamine receptor has been purified 21500 fold from bovine striatal membranes. Solubilized receptor preparation was partially purified by affinity chromatography on a haloperidol adsorbent followed by gel filtration on a Sephacryl S-300 column. The fractions eluted from this column which contained the ligand binding activity were further chromatographed on wheat germ agglutinin conjugated to Sepharose. The resulting receptor preparation displays a major polypeptide band of an apparent molecular weight of 92 kDa, and exhibits a specific binding activity of 2490 pmol spiperone per mg protein. This purified receptor preparation can reabsorb specifically to the haloperidol affinity column indicating that the 92 kDa polypeptide represents the ligand binding unit of the D-2 dopamine receptor.

Animals↗
PubMed1988

Anti-idiotypes against a monoclonal anti-haloperidol antibody bind to dopamine receptor.

Anti-idiotypic antibodies were raised in rabbits by immunization with a monoclonal anti-haloperidol antibody. Some of these anti-idiotypic antibodies bind in a concentration dependent manner to bovine striatal membranes. Following affinity purification, these antibodies inhibit haloperidol binding to striatal membranes and deplete [3H]-spiperone binding sites from a solubilized preparation of striatal membranes. It is thus concluded that these anti-idiotypic antibodies are an internal image of haloperidol and as such can interact with D2-dopamine receptors.

Animals↗
PubMed1988

Antibodies against haloperidol specific to the butyrophenone moiety.

Polyclonal and monoclonal antibodies to the D2-dopamine receptor antagonist haloperidol were produced by immunization with haloperidol conjugated to bovine serum albumin either through the tertiary hydroxy group of the piperidine ring (halo(OH)-BSA), or through the keto group of the butyrophenone (halo(CO)-BSA). Polyclonal rabbit antisera raised against halo(OH)-BSA exhibited high affinity for [3H]haloperidol. A fraction of these antibodies also bound [3H]spiperone with high affinity. Inhibition of the [3H]spiperone binding by various butyrophenone derivatives displayed a specificity similar to that observed for the inhibition of [3H]spiperone binding to the D2-dopamine receptor. Both monoclonal antibodies raised against halo(CO)-BSA(AG-58) and against halo(OH)-BSA(AC-91) exhibited high binding affinities to haloperidol. Monoclonal antibody AG-58 cross-reacted primarily with butyrophenone derivatives that are closely related to haloperidol in their substitutions on the piperidine ring. On the other hand, monoclonal antibody AC-91 cross-reacted with a wide range of butyrophenones with binding specificities resembling those of the dopamine receptor.

Animals↗
PubMed1985

Role of the pulvinar-lateralis posterior nucleus complex (P-LP) in the experimental epilepsy of the cat.

The ability of the pulvinar-lateralis posterior nucleus complex (P-LP) to evoke epileptic activity when stimulated, was studied in 20 adult cats. Twelve animals were analyzed after they recovered from the surgical procedure (chronic model). In seven of them a cannula with electrodes was implanted in the P-LP and one twisted bipolar electrode was placed ipsilaterally in the following structures: hippocampus, superior colliculus, caudate nucleus and cerebral cortex. Through the cannula Na penicillin was injected. The electrodes allowed both to stimulate and to record the electrical activity. In the remaining five cats, the cannula was implanted in hippocampus in order to compare its sensitivity to generate epileptic activity to that of P-LP. Another group of eight cats were surgically implanted and studied in the same day (acute model). In four of them the cannula was placed in the P-LP through the temporal pathway, to avoid crossing the hippocampus and the ventricle. In another four, penicillin was injected in the P-LP after suctioning the cerebral cortex and the hippocampus overlying the former structure. Epileptic activity could be induced in P-LP and it spread rapidly to hippocampus and after a while to the other implanted structures. This was observed both with penicillin and electrical stimulation. The sensitivity of P-LP to generate epileptic activity was lower than that of the hippocampus. In particular, it was necessary to use two to ten times more penicillin and three times the electrical current intensity in the P-LP as compared to the values needed in the hippocampus. These results are discussed in view of the controversial problem about the ability of the thalamus to generate and spread epileptic activity.

Animals↗
PubMed1982

Local electrographic effects of leu-enkephalin microinjections into the brain.

Microinjections of Leu-enkephalin were made in dorsal hippocampus, caudate nucleus, amygdala, nucleus accumbens and parietal cortex in rats. The effects of enkephalin on the local electrical activity recorded from the area of the microinjection are described. Depression effects (attenuation of amplitudes and slowing) were recorded in caudate nucleus, nucleus accumbens, amygdala and parietal cortex, but not in hippocampus. Activation and epileptiform effects (spikes, seizures) were recorded from all structures studied.

Animals↗
PubMed1981

Influence of body temperature on the epileptogenic effect of enkephalin microinjections into the hippocampus.

The influence of different body temperatures on the epileptiform discharges induced in hippocampus by local microinjections of leu-enkephalin was studied in rats. In the absence of enkephalin, changes in body temperature by either cooling or heating induced epileptiform discharges that disappeared after temperature stabilization. The epileptiform episode induced by enkephalin microinjections was of longer duration at temperature below normal (29-30 degrees C). At body temperature above normal (39-40 degrees C) the epileptiform discharge was less intense and of shorter duration. In vitro testing led to parallel results: the destruction of enkephalin by the brain tissue was faster at higher temperatures. It is proposed that in conditions of hyperthermia enkephalin has a weaker activity due to acceleration of the activity of peptidases involved in its breakdown.

Animals↗