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H D Fischer

Publications and source records attributed to H D Fischer.

At least 73 records · Page 4Linked to original sources
PubMed1981

[Effect of ethanol on the behavior of mice treated with haloperidol].

Ethanol interacts with several central transmission systems. Following ethanol application we observed an inhibition of locomotion, vigilance and muscle tone in a modified Irwin-behaviour test. The effect was strengthened by a single dose of haloperidol. Contrary to this observation the ethanol effects decreased when haloperidol was given repeatedly for weeks before the application of ethanol. Three days after haloperidol withdrawal in case of nearly complete haloperidol elimination and development of dopaminergic supersensitivity the decrease was most pronounced. The results indicate that ethanol effects on dopaminergic functions are weakened in consequence of an increased efficiency of the adequate transmission system and vice versa.

Animals↗
PubMed1980

Phosphomannosyl-enzyme receptors in rat liver. Subcellular distribution and role in intracellular transport of lysosomal enzymes.

beta-Hexosaminidase B purified from human fibroblast secretions was used as a ligand to study phosphomannosyl-enzyme receptors in membranes from rat tissues. Enzyme binding to rat liver membranes was saturable, competitively inhibited by mannose 6-phosphate, not dependent on calcium, and destroyed by prior treatment of the hexosaminidase with either alkaline phosphatase or endoglycosidase H. Most (90%) of the phosphomannosyl-enzyme receptors were found in endoplasmic reticulum, Golgi apparatus, and lysosomes; 9.5% in the plasma membrane, and less than 1% in nuclei and mitochondria. Receptors were vesicle-enclosed in all fractions except plasma membrane. Receptors in the endoplasmic reticulum apparently were occupied by endogenous ligands, but most receptors in lysosomes and plasma membrane were unoccupied. Most of the endogenous beta-hexosaminidase was in lysosomes and was released from vesicles by detergent treatment. Displacement of the residual receptor-bound endogenous beta-hexosaminidase (mostly in endoplasmic reticulum and Golgi apparatus) from detergent-treated membranes by mannose 6-phosphate released high uptake enzyme with properties expected for phosphomannosyl-enzymes. Mannose 6-phosphate-inhibitable enzyme receptor activity was found in nine rat organs and correlated roughly with their lysosomal enzyme content. These data support a general model for lysosomal enzyme transport in which the phosphomannosyl-enzyme receptor acts as a vehicle for delivery of newly synthesized acid hydrolases from the endoplasmic reticulum to lysosomes.

Animals↗
PubMed1980

The influence of haloperidol pretreatment on the morphine toxicity.

The influence of dopaminergic modifiers on morphine-induced analgesia and lethality was studied comparing both the effect of a single pre-dose of haloperidol and and continuous pretreatment for three weeks with haloperidol. A single administration of haloperidol enhanced morphine-induced analgesia probably due to the receptor blocking action of haloperidol which supports the reduction of dopamine release produced by morphine. The daily haloperidol administration for 3 weeks however decreased the analgesic action of morphine in consequence of a dopamine receptor supersensitivity developed in this time. The lethality was increased under both conditions. These results suggest that the dopaminergic system, dependent upon its sensitivity, plays a modulating role in morphine-induced analgesia, but not in morphine-induced lethality.

Analgesics↗
PubMed1980

Fibroblast receptor for lysosomal enzymes mediates pinocytosis of multivalent phosphomannan fragment.

Mild acid hydrolysis of phosphomannan secreted by the yeast hansenula holstii (NRRL Y- 2448) produces two phosphomannyl fragments which differ strikingly in their potency as inhibitors of pinocytosis of human beta-glucuronidase by human fibroblasts. The larger molecular weight polyphosphomonoester fragment is 100,000-fold more potent an inhibitor of enzyme uptake than the smaller penta-mannosyl-monophosphate fragment. Binding to attached fibroblasts at 3 degrees C was much greater with the polyphosphomonoester fragment than with the pentamannosyl-monophosphate. The larger molecular weight fragment was also subject to adsorptive pinocytosis and was taken up by fibroblasts at a rate 30- fold greater than the rate of uptake of pentamannosyl-monophosphate. Evidence that the polyphosphomonoester fragment is taken up by the phosphomannosyl-recognition system that mediates uptake of lysosomal enzymes includes: (a) its pinocytosis is inhibited by the same compounds that competitively inhibit enzyme pinocytosis (mannose-6-phosphate and phosphomannan from saccharomyces cerevisiae mutant mnn-1); (b) alkaline phosphatase treatment greatly reduces its susceptibility to pinocytosis; (c) its pinocytosis is competitively inhibited by high-uptake human beta-glucuronidase; and (d) this inhibition by high-uptake enzyme is dramatically reduced by prior treatment of the enzyme with alkaline phosphatase or endoglycosidase-H. Endoglycosidase-H treatment human beta-glucuronidase dramatically reduced its susceptibility to pinocytosis by fibroblasts. The phosphomannosyl components of high- uptake enzyme released by endoglycosidase-H treatment were much less effective inhibitors of polyphosphomonoester pinocytosis than when present on the phosphomannyl-enzyme. These results suggest that high-uptake acid hydrolases may be polyvalent ligands analogous to the polyphosphomonoester mannan fragment whose pinocytosis depends on interaction of more than one phospho-mannosyl recognition marker with pinocytosis receptors on fibroblasts.

Alkaline Phosphatase↗
PubMed1980

[Effect of reserpine on monoamine uptake by rat brain synaptosomes].

With regard to the inhibition of monoamine-uptake the concentration response curve of reserpine shows a biphasice turn. The first phase produces a maximum dopamin-uptake inhibition of 55% (EC50:8 X 10(-9) mol X 1(-1)) which is of a competitive manner only in the presence of a very low reserpine concentration (1 X 10(-9) mol X 1(-1)). Higher concentrations of reserpine inhibit the dopamine-uptake non competitively. This specific irreversible vesicular reserpine effect used therapeutically forms a plateau within a concentration rank from 10(-7) mol X 1(-1) to 10(-5) mol X 1(-1). A second mode of action of reserpine affects obviously the carrier mechanism located at the synaptosomal membrane (EC50: 5 X 10(-5) mol X 1(-1)). This second phase differs both from the first vesicular reserpine effect and from the synaptosomal action of tricyclic antidepressant drugs by its kinetic behavior (Km, Vmax).

Animals↗
PubMed1980

[Effect of psychodrugs on morphine effectivity (author's transl)].

After withdrawal of daily treatment with haloperidole (2 mg/kg s.c.) and apomorphine (10 mg/kg s.c.) for 21 days, respectively, and clomipramine (15 mg/kg s.c.) for 28 days, a decrease of morphine analgesia is observed. The findings are interpreted as a sensitivity change of the transmission systems involved in the action mechanism of the antinocifensive morphine effect. Morphine lethality remains unaffected by the synaptic efficiency of the transmission systems investigated.

Analgesia↗
PubMed1980

Interaction at the synaptic level of fusaric acid with neurotransmitters.

Fusaric acid (FA) is shown to induce inhibition of noradrenaline and dopamine uptake in synaptosomes from rat hypothalamus and corpus striatum. The basal overflow of noradrenaline and dopamine from "brain stem" and corpus striatum slices is stimulated by FA. While this influence of FA on noradrenaline release is further enhanced by other stimuli (raised K+ concentration or electrical stimulation), no comparable effect can be observed concerning dopamine release. The data show that FA which is known as a potent dopamine-beta-hydroxylase inhibitor of high specificity exerts also marked effect in the central nervous system by interference with other synaptosomal functions.

Animals↗
PubMed1978

[Influence of duration and depth of ether of brevinarcon narcosis on the cerebral acetylcholine content of rat].

For decapitation of rats in order to determine brain acetylcholine (Ach) content the animals may be anaesthesized slightly by ether no longer than for 2 min, since forebrain Ach content increases quickly up to about 170% throughout the following 3 min. The progress of brain Ach content up to its maximum level is decided both by duration and degree of cns depression: In the moment of most distinctly marked Brevinarcon -narcosis -- evident 2,5 min after i. v. injection (40 mg/kg) -- the forebrain Ach content merely is increased by about 15%, but when anaesthesia is reduced considerably again -- 2,5 min later -- the Ach content only reaches its maximum level.

Acetylcholine↗
PubMed1978

[Fluorescence-analytical studies of the reaction of several psychoactive drugs with membrane structures of the CNS].

The use of 1-anilino-8-naphthalene sulfonate (ANS) as an indicator of membrane conformational perturbations induced by psychoactive drugs was tested with regard to its specificity considering both chemical structure (phenothiazine, butyrophenone, phenylalkylhydrazine) and pharmacological activity (major transquilizers, antidepressants, antihistamines), on the one hand, and brain region (cortex, striatum, hippocampus) and subcellular structure of membranes (mitochondria, microsomes, synaptosomes), on the other. Not only a weak strengthening of ANS affinity to membrane constituents by chlorpromazine and promethazine (haloperidol and phenelzine were without effect), but also the alteration of membrane structure in such a way as to create additional ANS binding sites by chlorpromazine and to a smaller degree also by promethazine and haloperidol (phenelzine was without effect) resulting in a manifold increase in fluorescence indicated any relation to functional characteristics of biological material or properties of drugs. Apparent dissociation constants and membrane ANS binding sizes are reported.

Anilino Naphthalenesulfonates↗
PubMed1977

Brain acetylcholine, adenine nucleotides and their degradation products after intraperitoneal and intracerebral adenosine administration.

The paper describes adenosine effects on the acetylcholine synthesis and the profiles of adenine nucleotides, adenosine, inosine, and hypoxanthine in the rat brain in vivo after intracerebral (intraventricular) and intraperitoneal administration of adenosine. Intracerebral as well as extracerebral adenosine injection caused a dose- and time-dependent increase of the cerebral acetylcholine level, which was not accompanied by an equal development of the contents of adenine compounds and their degradation products. However, a considerable turnover of adenosine was observed in the brain after both routes of administration concerning the nucleotide as well as the degradation pathway. The kinetics of the purified enzymes of choline acetyltransferase and acetylcholinesterase were not influenced by adenosine. By this, the adenosine-caused increase of the cerebral acetylcholine cannot be explained by a direct molecular attack of adenosine on the enzymes of the synthesis or degradation of acetylcholine. An indirect mechanism which includes cAMP was discussed as a possible interpretation at present.

Acetylcholine↗
PubMed1976

Effect of arecoline on synaptosomal K+-phosphatase and (Na+ + K+)-ATPase.

Synaptosomal fractions and synaptosomal membranes from rat brain tissue were prepared and characterized enzymatically. Arecoline increased both the activity of K+-phosphatase in incubated synaptosomal fractions and the (Na+ + K+)-ATPase activity of synaptosomal membranes by 40% and 78%, respectively. This activation of ion transport processes is believed to be associated with increased ACh synthesis produced by arecoline.

Acetylcholine↗
PubMed1976

[Influence of strophanthin and 2,4-dinitrophenol to the scopolamine-evoked acetylcholine release in rat cortex].

In rats narcotized by urethan we investigated the effect of 2,4-dinitrophenol and ouabain with regard to the cortical release of acetylcholine stimulated by scopolamine and to the acetylcholine content of telencephalon changed in that way. Dinitrophenol increased the liberating effect of scopolamine. In the presence of dinitrophenol and scopolamine ouabain reduced acetylcholine synthesis resulting in an strong decrease of acetylcholine content on persistent diminished increase of acetylcholine release.

Acetylcholine↗