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H Zimmermann

Publications and source records attributed to H Zimmermann.

At least 181 records · Page 10Linked to original sources
PubMed1994

Signalling via ATP in the nervous system.

Strong evidence has been provided that ATP can act as a transmitter not only in smooth muscle but also in peripheral ganglia and in brain. The cloning and molecular identification of two putative ATP receptors supports the previously established pharmacological receptor classifications. This review places into perspective the evidence for ATP as a neural signalling substance by examining sites of storage, release and hydrolysis, as well as potential actions and targets. The action of ATP is related to that of the nucleoside adenosine, and the potential of additional nucleotides to function as neural messenger is examined briefly.

Adenosine Triphosphate↗
PubMed1994

Effects of heavy ions on inactivation and DNA double strand breaks in Deinococcus radiodurans R1.

Inactivation and double strand break (dsb) induction after heavy ion irradiation were studied in stationary phase cells of the highly radiation resistant bacterium Deinococcus radiodurans R1. There is evidence that the radiation sensitivity of this bacterium is nearly independent on energy in the range of up to 15 MeV/u for lighter ions (Ar). The responses to dsb induction for charged particles show direct relationship between increasing radiation dose and residual intact DNA.

Argon↗
PubMed1994

Effect of development on the functional and histological changes induced by bile-duct ligation in the rat.

Secondary biliary cirrhosis in the rat can be induced by bile duct ligation; the aim of the present study was to investigate whether susceptibility to this injury depends on development. Rats aged 4, 7, 14 and 22 weeks were bile-duct ligated or sham operated. Four weeks later, stereologic analysis of the liver was performed and the volume fraction of parenchyma, bile ducts and connective tissue was determined. Microsomal function was assessed in vivo by the aminopyrine breath test and in vitro by determining the microsomal cytochrome P450 content and microsomal lipid composition. In addition, portal pressure was measured. The volume fraction of parenchyma decreased in an age-dependent fashion in bile-duct ligated rats from 64.0 +/- 11.2% in the youngest to 46.4 +/- 8.4% in the oldest age group. This decrease was compensated by an age-dependent increase in both ductular proliferation and fibrosis. Microsomal function both in vivo and in vitro showed an age-dependent deterioration. Microsomal cholesterol and some individual phospholipids showed age-dependent changes. Portal hypertension developed in all bile-duct ligated groups, but portal pressure was significantly lower in the oldest bile-duct ligated groups (16.0 +/- 2.6 cmH2O) compared with other bile-duct ligated groups (around 21 cmH2O). We conclude that susceptibility to the sequelae of chronic cholestasis depends on the stage of development in rats. In experiments using this model, the age of the rats should be explicitly stated.

Age Factors↗
PubMed1994

SV2 and o-rab3 remain associated with recycling synaptic vesicles.

o-rab3 is an electric ray homologue of low molecular weight of GTP-binding proteins thought to be involved in targeting of secretory vesicles to sites of exocytosis. The stimulation-dependent association of o-rab3 with synaptic vesicles was compared with that of the membrane-integral synaptic vesicle protein 2 (SV2). On application of immunoelectron microscopy and the colloidal gold technique, antibodies against either protein labeled the synaptic vesicle membrane compartment. Synaptic vesicles recycled under conditions of low frequency stimulation (0.1 Hz) retained their complement of both SV2 and o-rab3. Isolation of synaptic vesicles by density-gradient centrifugation and subsequent column chromatography yielded no indication of a stimulation-dependent release of o-rab3 from synaptic vesicles. In contrast, multivesicular bodies and vacuoles occasionally observed in the nerve terminals contained SV2 but little if any o-rab3. It is concluded that o-rab3 remains associated with the synaptic vesicle membrane compartment during stimulation-induced cycles of repeated exo- and endocytosis. o-rab3 may be lost once the vesicle enters the prelysosomal pathway.

Animals↗
PubMed1994

Putative synaptic vesicle nucleotide transporter identified as glyceraldehyde-3-phosphate dehydrogenase.

Synaptic vesicles isolated from electric ray electric organ have been shown previously to contain a 34-kDa protein that binds azido-ATP, azido-AMP, and N-ethylmaleimide. The protein was found to share similarities with the mitochondrial ADP/ATP carrier and assumed to represent the synaptic vesicle nucleotide transporter. Synaptic vesicles were purified by sucrose density gradient centrifugation and subsequent chromatography on Sephacryl S-1000 from both Torpedo electric organ and bovine brain cerebral cortex. They contained ATP-binding proteins of 35 kDa and 34 kDa, respectively. ATP binding was inhibited by AMP. Both proteins were highly enriched after column chromatography of vesicle proteins on AMP-Sepharose. Antibodies were obtained against both proteins. Antibodies against the bovine brain synaptic vesicle protein of 34 kDa bound specifically to the 35-kDa protein of Torpedo vesicles. An N-terminal sequence obtained against the 34-kDa protein of bovine brain synaptic vesicles identified it as glyceraldehyde-3-phosphate dehydrogenase. The previously observed molecular characteristics of the putative vesicular nucleotide transporter in Torpedo fit those of glyceraldehyde-3-phosphate dehydrogenase. We, therefore, suggest that the protein previously identified as putative nucleotide transporter is, in fact, glyceraldehyde-3-phosphate dehydrogenase.

Amino Acid Sequence↗
PubMed1994

Projection of brain stem neurons to the giant electromotoneurons in the cervical spinal cord of the electric catfish Malapterurus electricus.

Two giant electromotoneurons located within the cervical spinal cord form the centerpiece of the electromotor system in the electric catfish Malapterurus electricus. The cytoarchitectural organization suggests a high degree of input convergence onto the electromotoneurons. In order to obtain insights into the connectivities of the electromotor system, pre-neurons of the electromotoneurons within the brain stem and the spinal cord were labelled by application of FITC-dextran and horseradish peroxidase onto the surface of a single electromotoneuron. Our results show that the electromotoneurons receive their main inputs from the nucleus profundus mesencephali within the tegmentum and from large neurons of the medial reticular formation. Both nuclei possess an intimate connection to the optic tectum which mediates orientation responses. This pathway to the electromotoneurons could be instrumental in eliciting electric organ discharge during prey catching. The electric avoidance response in turn could be mediated by the Mauthner neurons which are also labelled. In addition to these neurons, cells of the nucleus fasciculi longitudinalis medialis, the descending octaval nucleus and the nucleus funicularis medialis were labelled. As compared to the corresponding neurons in ictalurid catfish, none of these neurons displays any alteration in its general morphology. It is concluded that the evolution of the electric organ from muscle tissue and the development of a central control system of the electromotor response in Malapterurus involved a minimum of alterations in central nervous system circuitry. In contrast to many other electric fishes the electromotor control is mainly accomplished at the level of the electromotoneurons.

Animals↗
PubMed1993

Transient association of the HNK-1 epitope with 5'-nucleotidase during development of the cat visual cortex.

During early postnatal development of the kitten visual cortex the ectoenzyme 5'-nucleotidase undergoes a characteristic redistribution. Until about postnatal week 6 it is essentially confined to synaptic contacts in input layer IV and its expression is related to the use-dependent segregation of thalamic afferents into ocular dominance columns. Subsequently, 5'-nucleotidase becomes distributed uniformly throughout all layers and is then associated selectively with glial cells. Here we describe an age-dependent alteration in the expression of a carbohydrate epitope of 5'-nucleotidase which correlates with the developmental change of the enzyme's localization. We have isolated 5'-nucleotidase from the occipital cortex of kittens of varying age and from adult cats and investigated by immunoblotting the association of the HNK-1 carbohydrate epitope with the protein. 5'-Nucleotidase carries the HNK-1 epitope in kittens of 3-9 weeks but the epitope is absent from 12-week-old kittens or adult cats. Thus, the appearance of the HNK-1 epitope correlates with the transient localization of the enzyme at synapses. The HNK-1 carrying 5'-nucleotidase may be involved in synaptogenesis and use-dependent modifications of synaptic connections.

5'-Nucleotidase↗
PubMed1993

Isolation of a Ca2+ or Mg(2+)-activated ATPase (ecto-ATPase) from bovine brain synaptic membranes.

An ATPase was isolated from synaptosomal plasma membranes derived from bovine cerebral cortex. The protein has an apparent molecular mass of 50 kDa and a pI of 5.3 to 5.9. It can be labelled by incubation of intact synaptosomes with azido-GTP or azido-ATP. The isolated ATPase can be activated to a similar extent in the presence of millimolar concentrations of Mg2+ or Ca2+. It does not hydrolyze ADP. Maximal activity is obtained between pH 7.5 and 8.5. Typical inhibitors of cytoplasmic ATPases do not affect enzyme activity. The enzyme is specifically inhibited after previous incubation of intact synaptosomes in the presence of the slowly membrane-permeable enzyme inhibitor diazotized sulfanilic acid. Incubation of intact synaptosomes with diazotized sulfanilic acid results in a small increase in the apparent molecular mass of the enzyme. Our results suggest that the active site of the membrane bound enzyme faces the extracellular medium. It thus would represent an ecto-ATPase.

Adenosine Triphosphatases↗
PubMed1993

Selectivity of sterically fixed tryptamine and 5-methoxytryptamine derivatives for serotonin receptor subtypes, II: Structure-activity relationships and in vitro pharmacology of N-alkyl- and N,N-dialkyl-3- indolylbicyclo-[2.2.1]-heptane-2-amines.

Twenty-four norbornane analogues of tryptamine and 5-methoxytryptamine were investigated for affinity at 5-HT2 receptors of the rat tail artery and proved to be weak non-competitive antagonists of 5-HT. Compound 12 which displayed a marked depression of the concentration-effect curves, was examined for potential interaction with the allosteric binding site of the 5-HT2 receptor. The effects elicited by 12, in the presence and absence of the allosteric activator ketanserin, were atypical and must be attributed to a mechanism, unknown up to now. In radioligand displacement experiments binding data for a set of nine compounds were determined at 5-HT1-like, 5-HT2 and 5-HT3 receptors, indicating subtype selectivity for some analogues. The binding affinity of 8 at 5-HT3 receptors which was comparable with the affinity of the selective 5-HT3 agonist 2-methyl-5-HT, could not be demonstrated on the longitudinal muscle strip of the guinea-pig ileum, partially due to the M3 antimuscarinic activity of 8. Functional studies on the rat oesophageal tunica muscularis mucosae did not reveal 5-HT4 agonist properties for two analogues of 5-methoxytryptamine (8, 16).

5-Methoxytryptamine↗
PubMed1993

Cytoplasmic segregation and cytoskeletal organization in the electric catfish giant electromotoneuron with special reference to the axon hillock region.

The cytoplasm of the highly polarized nerve cell is permanently segregated into domains with differing organellar composition. The mechanisms maintaining this segregation are largely unknown. In order to elucidate the potential role of cytoskeletal elements in this process we compared the cytoplasmic segregation within the giant electromotoneuron of the electric catfish (Malapterurus electricus) with the distribution of binding sites for antibodies against elements of the cytoskeleton. Most prominent cytoplasmic segregations include the formation of a subplasmalemmal cortical structure free of Nissl bodies and Golgi cisternae, the separation within the soma of domains containing rough endoplasmic reticulum and filament-rich domains, and the soma-axon transition. The cytoplasmic transition at the axon hillock forms a distinct borderline where Nissl bodies, Golgi cisternae and the bulk of lysosomes abruptly terminate and are excluded from the axoplasm. Synaptic vesicles and mitochondria are free to pass compartmental borders. Tropomyosin, spectrin, and alpha-actinin reveal a rather homogeneous immunofluorescence throughout the neuron. In contrast, neurofilament protein and tubulin display a distinctly increased immunofluorescence in the subplasmalemmal cortical layer, in dendrites as well as in the axon. The increase in immunofluorescence at the axon hillock exactly depicts the small transition zone from the somatic cytoplasm rich in Nissl bodies, Golgi cisternae and lysosomes to the differently structured axoplasm. The picture is similar for beta-tubulin, tyrosinylated and detyrosinylated alpha-tubulin. Detyrosinylated tubulin (glu-tubulin, which is contained in microtubules of increased stability) shows the most prominent enrichment in the axon. The distribution of myosin is comparable to that of neurofilament protein but there is less difference in immunofluorescence between the domains. Our results would be compatible with a role of microtubules together with (the closely associated) neurofilaments in the segregation of neuronal cytoplasmic domains. Active transport as well as stable binding to the somatic cytoskeleton might counteract a homogeneous cytoplasmic distribution of the various classes of organelles by diffusion.

Actinin↗
PubMed1993

Hippocampal localization of 5'-nucleotidase as revealed by immunocytochemistry.

The distribution of binding sites for an antibody against ecto-5'-nucleotidase was investigated in the mouse hippocampus by light microscopical immunocytochemistry. The antibody selectively labels a band corresponding to the innervation area of mossy fibre terminals within area CA3. Area CA1 as well as the dendate gyrus are negative. In area CA3 only the proximal but not the distal parts of the apical dendrites of pyramidal cells are labelled. Labelling is in the form of large dots around dendrites of pyramidal cells suggesting that mossy fibre terminals are immunopositive. In contrast, an antibody against the ubiquitous synaptic vesicle protein SV2 labels the large mossy fibre terminals as well as fine and punctate structures in the dendritic and somatic regions throughout the hippocampus. Labelled astrocytes can be found in the entire hippocampus and are frequent in the stratum radiatum and stratum oriens of the CA1 region. Immunopositive astrocytic processes can be found in association with capillary walls. Our results suggest that ecto-5'-nucleotidase may play a crucial role in the hydrolysis of AMP to adenosine at the mossy fibre synapses. Thus, at these synapses, 5'-nucleotidases could function both in completing the extracellular hydrolysis of synaptically released ATP as well as in the extracellular formation of adenosine.

5'-Nucleotidase↗
PubMed1993

Synaptic vesicle life cycle and synaptic turnover.

Cholinergic synaptic vesicles contain a mixture of soluble low molecular mass constituents. Besides acetylcholine these include Ca2+, ATP, GTP, small amounts of ADP and AMP, and also the diadenosine polyphosphates Ap4A and Ap5A. In synaptic vesicles isolated from the electric ray these diadenosine polyphosphates occur in mmol concentrations and might represent a novel cotransmitter. The membrane proteins of cholinergic synaptic vesicles presumably are identical to those in other types of electron-lucent synaptic vesicles. A presumptive exception are the transmitter-specific carriers. The life cycle of the synaptic vesicle in intact neurons and in situ was investigated by analysis of all cytoplasmic membrane compartments that share membrane integral proteins with synaptic vesicles. The results suggest that the synaptic vesicle membrane compartment might originate from the trans-Golgi network and, after cycles of exo- and endocytosis in the nerve terminal, might fuse into an endosomal membrane compartment early on retrograde transport. Tracer experiments using membrane proteins and soluble contents suggest that the synaptic vesicle membrane compartment does not intermix with the presynaptic plasma membrane on repeated cycles of exo- and endocytosis if low frequency stimulation is applied. A cDNA has been isolated from the electric ray electric lobe that codes for o-rab3, a small GTP-binding protein highly homologous to mammalian rab3. While abundant in the nerve terminals of the electric organ and at the neuromuscular junction this protein occurs only in limited subpopulations of nerve terminals in electric ray brain. Immunocytochemical analysis using the colloidal gold technique and a monospecific antibody against o-rab3 suggests that the GTP-binding protein remains attached to recycling synaptic vesicles. No evidence was found for a major contribution of an intraterminal endosomal sorting compartment involved in synaptic vesicle recycling.

Acetylcholine↗
PubMed1993

Biliary retention in a chronic choledocho-venous fistula in the rat: induction of portal hypertension but not of biliary cirrhosis.

In this study we investigated whether the retention of compounds which are excreted into the bile could contribute to portal hypertension in secondary biliary cirrhosis. Choledochovenous fistulas were grown in rats for 4 weeks. 6/13 of the animals had biochemical evidence of partial obstruction. Microsomal function, as measured by the aminopyrine breath test, was decreased in all animals with biliary retention while microsomal cytochrome P-450 content was decreased only in rats with evidence of obstruction. All animals with biliary retention with or without partial obstruction had portal hypertension. Animals with biliary retention and partial obstruction had hypercholeresis but decreased bile salt excretion. All animals with a chronic catheter in the biliary tree had a loss of the negative permselectivity of the sinusoidal-canalicular barrier and decreased maximal bile secretory pressure. Only animals with biochemical evidence of obstruction had moderate fibrosis and ductular proliferation as determined by stereological techniques. Unexpectedly, morphometric analysis also revealed an increase in hepatocyte mass induced by biliary retention. We conclude that bile contains a compound(s) which induces portal hypertension. This putative substance is neither bilirubin nor a bile acid since portal hypertension was also observed in animals with biliary retention without obstructive signs.

Aminopyrine↗
PubMed1993

The synaptic vesicle-associated G protein o-rab3 is expressed in subpopulations of neurons.

The distribution of o-rab3--a synaptic vesicle-associated low-molecular-weight GTP-binding protein--was studied in various neural tissues of the electric ray Torpedo marmorata. o-rab3 was shown to be associated selectively with isolated cholinergic synaptic vesicles derived from the electric organ. Gel filtration of cholinergic synaptic vesicles using Sephacryl S-1000 column chromatography demonstrated a copurification of o-rab3 with the synaptic vesicle content marker ATP and with SV2--a synaptic vesicle transmembrane glycoprotein. Indirect immunofluorescence using antibodies against o-rab3 and SV2 and a double labeling protocol revealed an identical distribution of both antigens in the cholinergic nerve terminals within the electric organ and at neuromuscular junctions. An immunoelectron microscopic analysis demonstrated the presence of o-rab3 at the surface of the synaptic vesicle membrane. In the CNS immunofluorescence of o-rab3 and SV2 overlap only in small and distinct areas. Whereas SV2 has an overall only in small and distinct areas. Whereas SV2 has an overall distribution in nerve terminals of the entire CNS, o-rab3 is restricted to a subpopulation of nerve terminals in the dorsolateral neuropile of the rhombencephalon and in the dorsal horn of the spinal cord. Our results demonstrate that the synaptic vesicle-associated G protein o-rab3 is specifically expressed only in subpopulations of neurons in the Torpedo CNS.

Animals↗
PubMed1993

[Management of 2 cases of pseudarthrosis].

Authors describe their standpoint concerning the choice of therapeutic methods in the solution of two cases of the lower leg's pseudarthrosis. On the basis of two cases treated successfully they strive after osteogenetic induction and adequate stability and in the formation of principles after the equilibrium of modernity and rationality.

Adolescent↗
PubMed1993

[Basic reproductive toxicological studies of the effect of furazolidone on the hypothalamo-hypophyseo-gonadal axis of male rats].

The reproductive-toxic effects of furazolidone on testis, epididymis and selected nuclei of the hypothalamus of male wistar rats were investigated. After a dosage of 50 mg/kg b.w. daily over five days no changes of testis and epididymis were detected in relation to controls by means of light microscope. Using morphometric methods a significant increase of the nucleus volume of the measured nuclei of the hypothalamus (Ncl. ventromedialis, Ncl. praeopticus medialis, Ncl. infundibularis) could be shown. After the high dosage of 200 mg/kg b.w. daily for five days testis and epididymis showed marked signs of atrophy and the volume of the investigated nuclei of the hypothalamus was significantly increased. These results suggest that--contrary to the wide spread opinion the testis would react most sensitive to chemical agents--more attention should be directed to the hypothalamus in reproductive-toxicological studies.

Animals↗
PubMed1992

Purification and characterization of a pore-forming protein from the marine sponge Tethya lyncurium.

A pore-forming protein was detected and purified for the first time from a marine sponge (Tethya lyncurium). The purified protein has a polypeptide molecular mass of 21 kDa and a pI of 6.4. Tethya pore-forming protein (also called Tethya hemolysin) rapidly lysed erythrocytes from a variety of organisms. After binding to target membranes, the hemolysin resisted elution with EDTA, salt or solutions of low ionic strength and hence resembled an integral membrane protein. Erythrocytes could be protected from hemolysis induced by Tethya hemolysin by addition of 30 mM dextran 4 (4-6 kDa; equivalent hydrodynamic diffusion radius, 1.75-2.3 nm) to the extracellular medium, but not by addition of uncharged molecules of smaller size [sucrose, raffinose and poly(ethylene glycol) 1550; equivalent hydrodynamic diffusion radii, 0.46, 0.57 and 1.2 nm, respectively]. This result indicates that hemolysin is able to form stable transmembrane pores with an effective diameter of about 2-3 nm. Treatment of osmotically protected erythrocytes with Tethya hemolysin caused a rapid efflux of intracellular K+ and ATP, and a rapid influx of extracellularly added Ca2+ and sucrose. In negative-staining electron microscopy, target erythrocyte membranes exposed to purified Tethya hemolysin displayed ultrastructural lesions but without visible pores.

Adenosine Triphosphate↗