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K Hauser

Publications and source records attributed to K Hauser.

At least 37 records · Page 2Linked to original sources
PubMed1996

[ECG abnormalities in Airedale terriers].

Because of bradyarrhythmic complications under anesthesia in two Airedale Terriers, we performed a prospective search of ECG-abnormalities in healthy dogs of that breed. Resting ECG's were screened for routine abnormalities. None of the 42 dogs investigated so far had a completely normal ECG. Among the common abnormalities were: deviation of the mean electrical axis (MEA) in 32 dogs, low voltage QRS-complexes in 22 dogs, and AV-blocks 1st degree in 14 dogs. None of the recorded abnormalities with the exception of AV-blocks, were considered predictors of anesthetic complications. Because of the high frequency of recorded abnormalities, we are continuing this prospective study.

Anesthesia↗
PubMed1991

Saccharomyces cerevisiae a- and alpha-agglutinin: characterization of their molecular interaction.

An O-glycosylated protein of approximately 18 kDa responsible for mating type specific agglutination has been isolated from Saccharomyces cerevisiae a cells, purified to homogeneity and via peptide sequences the gene was cloned by PCR. An open reading frame codes for a protein of 69 amino acids. A minimum of five serine and five threonine residues of the mature protein are glycosylated. alpha-Agglutinin is a highly N-glycosylated protein of approximately 250 kDa. Both purified agglutinins form a specific 1:1 complex in vitro. Pretreatment of alpha-agglutinin, but not of alpha-agglutinin, with diethylpyrocarbonate (DEPC) prevents formation of the complex; treatment of alpha-agglutinin in the presence of alpha-agglutinin protects the former from DEPC inactivation. By carboxy terminal shortening of the alpha-agglutinin gene and by replacing three of its eight histidyl residues by arginine, the active region of alpha-agglutinin for interaction with alpha-agglutinin has been defined. Neither the N- nor the O-linked saccharides of the two agglutinins seem to be essential for their interaction.

Base Sequence↗
PubMed1990

CGP 28014, a new inhibitor of cerebral catechol-O-methylation with a non-catechol structure.

CGP 28014 (N-(2-pyridone-6-yl)-N',N'-di-n-propylformamidine) or its methanesulfonate salt CGP 28014 A was suspected to be a catechol-O-methyl-transferase (COMT) inhibitor because it was found to reduce the levels of homovanillic acid (HVA) and to increase those of 3,4-dihydroxyphenylacetic acid (DOPAC) in the rat striatum, after oral or intraperitoneal administration. These effects were maintained after repeated administration. The compound was only weakly active as a COMT inhibitor in vitro. However, its effect on striatal HVA and DOPAC was not prevented by pretreatment with the inhibitor of microsomal drug metabolizing enzymes in the liver, proadifen, indicating that, if CGP 28014 acts as a prodrug, its conversion to the active compound is not by oxidative metabolism in the liver. Also, there was no evidence that conversion to 2-amino-6-hydroxypyridine could explain its effects. The in vivo effect of CGP 28014 was substantiated in two additional in vivo test systems. Thus, it inhibited the accumulation of 3-methoxytyramine in the rat striatum after MAO inhibition by clorgyline, and the formation of O-methyl-DOPA from exogenously administered DOPA. It proved to be equipotent or nearly so with tropolone, and also showed a similar duration of action. Similar to tropolone, it increased S-adenosylmethionine levels in the striatum. Pyrogallol, on the other hand, decreased them, because being a substrate of COMT, it consumes methyl groups. This suggests that CGP 28014 does not inhibit COMT because it is a substrate of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Reversal by apomorphine of the gabaculine-induced GABA accumulation in mouse cortex.

To test the assumption that in the mice cortex the rate of accumulation of gamma-aminobutyric acid (GABA) after irreversible inhibition of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T) represents an index of GABA turnover, we examined whether the reversal of the gabaculine-induced accumulation of GABA elicited by apomorphine was due to a decrease in GABA turnover or to a modulation of the activity of the GABA-T inhibitor. Therefore, we simultaneously measured the action of apomorphine on gabaculine-induced accumulation of GABA and on GABA-T activity. In vitro, apomorphine (3 and 30 microM) did not alter the concentration-dependent inhibition of GABA-T by gabaculine. Ex vivo, apomorphine (2 x 0.5 mg/kg s.c.) markedly decreased (69%) gabaculine-induced (150 mg/kg i.p.) accumulation of GABA. This drug had no direct effect on GABA-T activity, but significantly reduced from 83 to 71% the inhibition of GABA-T by gabaculine. The linear correlation found between GABA levels and GABA-T activity allowed the quantification of the decrease in GABA turnover elicited by apomorphine. The results showed that apomorphine decreased significantly (P less than 0.001) the rate of GABA synthesis from 7.48 to 3.36 micromol GABA/g per h, if the partial reversal of gabaculine-induced inhibition of GABA-T is considered and 2.44 micromol/g per h if not. Apomorphine effect on GABA accumulation is mainly due to a decrease of the rate of GABA synthesis and to a lesser extent to a reversal of the inhibitory activity of gabaculine. Thus, inhibition of GABA-T by gabaculine is a sensitive and reliable method for the estimation of the rate of synthesis.

4-Aminobutyrate Transaminase↗
PubMed1989

CGP 31358 binds to a site on the NMDA receptor that is coupled to both the transmitter recognition site and the channel domain.

CGP 31358, a novel triazole, inhibited the binding of L-[3H]glutamate and [3H]MK-801 to the N-methyl-D-aspartate (NMDA) receptor complex in rat brain synaptic membrane fractions, and showed anticonvulsant activity in mice. It had no effect on the strychnine-insensitive binding of [3H]glycine. Saturation and Hill analyses indicated that CGP 31358 binds to a site on the NMDA receptor which is separate from, but coupled to, both the transmitter recognition site and the channel domain. Available data indicate that this site is distinct from those with which tricyclic antidepressants and ifenprodil interact. CGP 31358 is a new chemical entity with a novel mechanism of action at the NMDA receptor, and as such may form a tool for understanding the molecular pharmacology of this receptor-channel complex.

Animals↗
PubMed1989

Purification of the inducible alpha-agglutinin of S. cerevisiae and molecular cloning of the gene.

The alpha-agglutinin responsible for mating type-specific agglutination of S. cerevisiae alpha-cells has been purified to homogeneity. The glycoprotein released from the cell surface under mild conditions has a relative molecular mass of 200 to 300 kDa as determined by SDS-gel electrophoresis. The protein moiety corresponds to 68.2 kDa. With an oligonucleotide corresponding to the N-terminal amino acid sequence, the alpha-agglutinin gene has been cloned and sequenced. From the DNA sequence, a protein of 631 amino acids with 12 potential N-glycosylation sites is predicted. The carboxy terminal one-third of the protein is not required for agglutination activity.

Agglutination↗
PubMed1988

Fibrinogenolysis in the absence of fibrin formation in severe hypobaric hypoxia.

Acute exposure to hypoxia causes acceleration of activated partial thromboplastin time (aPTT) and a rise in factor VIII precoagulant activity (F VIII:C). To determine whether this activation of coagulation leads to in vivo fibrin formation we investigated 15 army pilots before and at the end of 21 min (range 14-29) of hypobaric hypoxia. Mean final pressure in the decompression chamber was 283 (250-310) mm Hg causing a fall in oxygen saturation to 61.5% (53-69). Hypobaric hypoxia caused acceleration of thrombin time (p less than 0.05), aPTT (p less than 0.01), and euglobulin lysis time (p = 0.05), as well as a rise of F VIII:C (p less than 0.05), beta-thromboglobulin (p less than 0.005), fibrin(ogen) degradation products E (p less than 0.005) and B beta 15-42 (p less than 0.001), as well as lactate (p less than 0.001). Fibrinopeptide A, a marker of in vivo fibrin formation, did not change significantly. It is concluded that severe hypoxemia due to rapid decompression going to the limit of tolerance does not lead to fibrin formation, whereas the rise in fibrin(ogen) degradation products demonstrates activation of the fibrinolytic system.

Adult↗
PubMed1987

Topography of substantia nigra innervation by D1 receptor-containing striatal neurons.

Iodinated SCH 23390, [125I]SCH 23982, saturably binds in brain to D1 receptors that mostly reside on striatal and striatonigral neurons. [125I]SCH 23982 autoradiography was used to determine the topography of D1 receptor-containing striatal inputs to subregions of the substantia nigra. The concentration of D1 sites was greatest in the pars reticulata of the substantia nigra and exceeded by over 50% the equal concentrations of D1 sites in the lateral substantia nigra, caudate-putamen, nucleus accumbens, and olfactory tubercle. D1 receptors were uniformly concentrated throughout the caudate-putamen and were absent in the pars compacta of the substantia nigra and ventral tegmental area. Injections into the rostral striatum of the axon-sparing neurotoxin, quinolinic acid, depleted the concentration of D1 sites in the rostral caudate-putamen by 98% and the concentration of D1 sites in the medial substantia nigra by up to 74%. Quinolinic acid-induced losses of the D1 sites in the central striatum of up to 85% were associated with 87% losses of D1 sites in the central nigra. D1 losses of 91% in the caudal striatum were associated with D1 losses of 85% in the lateral nigra. Thus, most D1 sites in the striatum reside on neurons that are intrinsic to that brain region, and the vast majority of D1 sites in the substantia nigra are on the terminals of striatonigral neurons. These D1 receptor-containing striatonigral neurons have a rostral, central, or caudal origin in the striatum and a corresponding medial, central, or lateral termination in the nigra. This topographical organization of striatal inputs to the substantia nigra indicates that substance P or dynorphin B-containing striatonigral neurons may have D1 receptors on their terminals.

Animals↗
PubMed1986

Ifoxetine, a compound with atypical effects on serotonin uptake.

Ifoxetine (CGP 15210 G; (+/-)-bis-[cis-3-hydroxy-4-(2,3-dimethyl-phenoxy)]-piperidine sulfate) prevented the depletion of serotonin (5-HT) induced by H 75/12 and p-chloromethamphetamine in the rat brain, and that caused by endogenously released dopamine after the combined administration of haloperidol and amfonelic acid in the rat striatum. These effects are typically caused by compounds that inhibit 5-HT reuptake. Unexpectedly, ifoxetine only weakly inhibited the uptake of radiolabelled 5-HT into rat brain synaptosomes in vitro or ex vivo, the human thrombocytes in vitro or into rat thrombocytes after pretreatment. The following, among the possible explanations for this apparent discrepancy, were considered and regarded as unlikely: the involvement of an active metabolite; the possibility that ifoxetine accumulates in the brain to an extent sufficient to cause in vivo uptake inhibition; a pharmacokinetic interaction with the depleting agents. The possibility that the depletor tests give false positives was also considered. However, ifoxetine lowered brain 5-hydroxyindoleacetic acid and reduced the accumulation of 5-hydroxytryptophan after central decarboxylase inhibition. This suggests that it also interferes with 5-HT metabolism in the absence of depleting agents, which means that it interacts in some way with serotonergic transmission. Ifoxetine displayed weak or no interactions with 5-HT1, 5-HT2, alpha 1-, alpha 2- and beta-noradrenoceptors, histamine H1, muscarinic acetylcholine, opiate, GABA A, and benzodiazepine receptors in vitro, and with dopamine and 5-HT2 receptors in vivo. It did not antagonize the noradrenaline (NA) depletion induced by H 77/77 in rat brain and only weakly interfered with the uptake of i.v. injected radiolabelled NA into the rat heart. This suggests that its interaction with the 5-HT system is specific. Due to its atypical properties, among which the rather weak potentiation of the neurological effects of 5-hydroxytryptophan is also important, ifoxetine may exhibit a therapeutic and/or side-effect profile which differs from that of classical 5-HT uptake inhibitors.

Animals↗
PubMed1985

Trimipramine, a tricyclic antidepressant exerting atypical actions on the central noradrenergic system.

Trimipramine is a tricyclic antidepressant which has only weak effects on noradrenergic systems. Its mechanism of action is not understood, but its clinical effectiveness has been proven over a period of 20 years. In the present investigation, trimipramine was shown to have no effect on noradrenaline (NA)-stimulated adenylate cyclase activity after either acute or once daily application for 28 days. There was no change in the KD or Bmax of [3H]DHA binding, demonstrating a lack of effect on beta-adrenergic receptors. However, it did exert effects on the cortical noradrenergic projection of the locus coeruleus and these effects were opposite to those described for typical antidepressants. In acute experiments, systemic injections of trimipramine potently activated locus coeruleus neurons and produced a reduction in the depressant action of noradrenaline administered iontophoretically to neurons in the cingulate cortex. After 4 weeks' treatment with a daily injection of 30 mg/kg i.p. trimipramine, cingulate cortical neurons became supersensitive to the action of iontophoretically applied noradrenaline. Although it is unknown whether these effects are related to the therapeutic efficacy of trimipramine, the results demonstrate that the down-regulation of central noradrenergic sensitivity in the rat is not a prerequisite for clinical efficacy of antidepressants in man.

Action Potentials↗
PubMed1985

Effects of subchronic administration of psychoactive substances on the circadian rhythm of urinary corticosterone excretion in rats.

Abnormal function of the hypothalamo-pituitary-adrenocortical (HPA) axis has been observed in depressed patients. Experiments with laboratory rats were performed to test whether psychoactive substances (among them clinically effective antidepressants) influence circadian HPA activity. For this purpose, corticosterone was measured in urine collected for 24 h at 4 h intervals. Maprotiline, fluoxetine, imipramine, trimipramine, clorgyline and pargyline were given once daily for at least 13 days, by either intraperitoneal or subcutaneous (clorgyline) injection. Only two substances produced significant changes in the circadian pattern of corticosterone excretion: pargyline distinctly delayed the phase of circadian HPA activity, and trimipramine prolonged the nocturnal increase in urinary corticosterone. The present results suggest that psychoactive drugs have no effects in common on the circadian rhythm of HPA activity in rats.

Animals↗
PubMed1984

Protective effects of diazepam and valproate on beta-vinyllactic acid-induced seizures.

GABA level and the activity of L-glutamate-1-decarboxylase (GAD) (EC 4.1.1.15) were studied in brains of mice treated with beta-vinyllactic acid, a new, selective and pyridoxal phosphate-independent GAD inhibitor. Valproate and diazepam protected mice against convulsions caused by beta-vinyllactic acid although both anti-epileptic drugs antagonized neither the decrease in GABA concentrations nor the inhibition of GAD observed after treatment with beta-vinyllactic acid alone. Assuming that the anticonvulsant effect measured with both antiepileptics is GABA mediated, these results support the hypothesis of a postsynaptic enhancement of GABAergic transmission by diazepam and valproate.

Animals↗
PubMed1984

Surface antigens of brain synapses: identification of minor proteins using polyclonal antisera.

Antigenic proteins of brain synaptic plasma membranes (SPM) and postsynaptic densities (PSD) were characterized using antisera raised against SPM. Immunostaining of brain sections showed that the antigens were restricted to synapses, and electron microscopy revealed staining at both presynaptic terminals and PSDs. In primary brain cell cultures the antisera were also neuron-specific but the antigens were distributed throughout the entire neuronal plasma membrane, suggesting that some restrictive influence present in whole tissue is absent when neurons are grown dispersed. The antigenic proteins with which these antisera react were identified using SDS gel immunoblots. SPM and PSD differed from one another in their characteristic antigenic proteins. Comparison with amido-black stained gel blots showed that in both cases most of these did not correspond to known abundant proteins of SPM or PSDs revealed by conventional biochemical techniques. None of the antigens revealed by the polyclonal antisera were detected by any of a large series of monoclonal antibodies against SPM.

Animals↗