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K Koschel

Publications and source records attributed to K Koschel.

At least 37 records · Page 2Linked to original sources
PubMed1987

[Volatile anesthetics and n-alcohols inhibit the uptake of noradrenaline in pheochromocytoma cells].

UNLABELLED: Studies with perfused animal organs did not show a significant inhibition of the norepinephrine uptake by volatile anesthetics However, the uptake of norepinephrine into isolated chromaffin granules proved to be halothane-sensitive , and there is indirect evidence for an inhibition of norepinephrine uptake by halothane in the dog saphenous vein. So far no literature is available on norepinephrine uptake into cultured cells in the presence of volatile anesthetics. The rat pheochromocytoma cell line PC 12, which shares many properties with adrenal medulla cells and also with sympathetic neurons, has been used as a model to study norepinephrine uptake and release. One of its properties in common with sympathetic neurons is the high-affinity uptake system for norepinephrine. Therefore, we have used PC 12 cells as a pharmacologically well-established model system to study the effect of general anesthetics on the uptake of norepinephrine. METHODS: The experiments were performed with monolayers of PC 12 cells on 3 cm petri dishes. The cells were allowed to take up tritiated norepinephrine (0.25 microCI/ml) for 20 min at 36 degrees C in the presence and absence of general anesthetics. RESULTS AND DISCUSSION: The volatile anesthetics halothane, enflurane, isoflurane, and methoxyflurane in clinical relevant concentrations inhibited the high-affinity uptake of tritiated norepinephrine into the PC 12 cells (Fig. 1). We could further show an inhibition of norepinephrine uptake by n-alkanols at concentrations that cause anesthesia in tadpoles. Fig. 2 illustrates that a good correlation (r = 0.997 for the n-alkanols, r = 0.934 for the volatile anesthetics) exists between anesthetic potency and the IC50 for norepinephrine uptake inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1986

Preliminary characterization of an Na+,K+,Cl- co-transport activity in cultured human astrocytes.

We have studied the potassium uptake using 86Rb+ into monolayers of secondary cultures of human astrocytes prepared from cerebral hemispheres of a 4-month-old fetus. With the use of inhibitors we could attribute 30-40% of the 86Rb+ uptake to an Na+,K+-ATPase, 50-60% to an anion-cation co-transporter and 10% to potassium leak channels. The anion-cation co-transporter was dependent on the simultaneous presence of both sodium and chloride in the incubation medium and is therefore most likely an Na+,K+,Cl- co-transporter. This is the first evidence of such an Na+,K+,Cl- co-transport in human astrocytes.

Animals↗
PubMed1985

Halothane inhibits the neurotoxin stimulated [14C]guanidinium influx through 'silent' sodium channels in rat glioma C6 cells.

We have investigated the effect of pharmacological agents on [14C]guanidinium ion influx through sodium channels in C6 rat glioma and N18 mouse neuroblastoma cells. The sodium channels of the N18 cells can be activated by aconitine alone, indicating that they are voltage-dependent channels. In contrast, sodium channels in the C6 cells require the synergistic action of aconitine and scorpion toxin for activation and are therefore characterized as so-called silent channels. The general anesthetic halothane used at clinical concentrations, specifically inhibited the ion flux through the silent sodium channel of C6 rat glioma cells. The voltage-dependent channels of the N18 cells were insensitive to halothane at the concentrations tested.

Aconitine↗
PubMed1985

Effect of measles virus antibodies on a measles SSPE virus persistently infected C6 rat glioma cell line.

Maintenance of measles (SSPE-Lec) virus persistently infected C6 rat glioma cells in medium containing polyclonal measles antiserum resulted in the loss of detectable expression of all measles virus proteins. Removal of these cells from antiserum, however, led to a re-expression of virus proteins and the production of infectious virus. Cloning of antibody-modulated non-expressing cells in the presence of antiserum showed that re-expression of virus proteins was not due to an incomplete curing process following the addition of antiserum, as a large number of non-expressing cell clones developed the capacity to express measles virus antigen at different periods after removal of antiserum. Irradiation of persistently infected cells to give a non-growing culture showed that modulation was not mediated by a selection and outgrowth of a small percentage of non-expressing cells originally present in the culture. Antibody directed against C6 membrane proteins did not lead to modulation and it was also shown that only monoclonal antibodies with neutralizing activity could affect intracellular antigen expression. Immunoglobulin Fab fragments with neutralizing activity also had modulating activity. Although all modulated cell clones were more susceptible to homologous virus infection than control C6 cells, it was not possible to rescue any defective measles virus which may have been maintained in the culture.

Animals↗
PubMed1984

Inhibition of opiate receptor-mediated signal transmission by rabies virus in persistently infected NG-108-15 mouse neuroblastoma-rat glioma hybrid cells.

Acute and persistent rabies virus infection of mouse neuroblastoma-rat glioma hybrid cells (NG-108-15) results in a loss of the normal inhibiting function of opiates via the opiate receptor on hormone-stimulated adenylate cyclase activity. Previous studies of these persistently infected cells have shown a decrease in the affinity of the opiate receptors for agonists without any change in the number of these receptors. We now demonstrate that persistently infected cells are unable to couple the opiate receptors to the inhibitory regulatory protein Ni of the adenylate cyclase, as measured by the loss of stimulation of the GTPase activity of this protein. However, the unstimulated basal GTPase activities of the regulatory components Ni and Ns are unchanged in the persistently infected cells. These studies also reveal a disorder of the stimulation of the adenylate cyclase by GTP or fluoride via the stimulating regulatory G/F protein (Ns) in persistently infected cells, whereas direct stimulation of the catalytic subunit of the adenylate cyclase by forskolin remains unchanged. Therefore, there are different points of dysfunction caused by the persistent rabies infection in the signal pathway from the opiate receptor to the adenylate cyclase and from the stimulating Ns protein to the enzyme: (i) opiate receptor binding is reduced by a decrease of agonist affinity (previously published data), (ii) the stimulation of GTPase activity of the inhibiting regulatory component Ni of the adenylate cyclase system is inhibited, and (iii) the signal pathway from the stimulating regulatory component of the adenylate cyclase system to the unchanged activity of the catalytic subunit is defective.

Adenylyl Cyclases↗
PubMed1983

Effect of antibody-induced modulation of measles (SSPE) virus membrane proteins on beta-adrenergic receptor-mediated adenylate cyclase activity.

The effect of measles virus antiserum on the expression of viral glycoproteins on the membranes of measles (SSPE) persistently infected C6 rat glioma cells was studied. There was a gradual loss of virus membrane antigen from these cells until no antigen was detectable 18 days after initiation of antiserum treatment. At this stage approximately 25% of cells still displayed intracellular virus antigen which was also lost after further cell passages. There was an accompanying recovery of the previously reported disrupted catecholamine-dependent beta-adrenergic receptor-stimulated cAMP synthesis in antiserum-treated cells which coincided with the loss of viral antigen from the membrane. This was determined to be due to a recovery of fluoride-stimulated activity of the cAMP synthesising adenylate cyclase enzyme to normal values. Thus we demonstrate that the impairment of this important cell function was due to insertion of viral antigen in the cell membrane rather than its accumulation in the cytoplasm.

Adenylyl Cyclases↗
PubMed1982

Alteration in phospholipid methylation and impairment of signal transmission in persistently paramyxovirus-infected C6 rat glioma cells.

The paramyxoviruses measles (subacute sclerosing panencephalitis, SSPE) virus and canine distemper virus (CDV) cause an impairment of the catecholamine-induced beta-adrenergic receptor-dependent cAMP generation in persistently infected C6 rat glioma cells. In C6 cells persistently infected with CDV the number of receptors is greatly reduced. Hirata and Axelrod have shown that the number of beta-adrenergic receptors could be regulated by methylation of phosphatidylethanolamine, resulting in lecithin synthesis [Hirata, F. & Axelrod, J. (1980) Science 209, 1082-1090]. We have therefore studied the methylation of phosphatidylethanolamine in persistently infected cells by the incorporation of [3H]methyl groups from [methyl-3H]methionine into phosphatidylethanolamine. In both infected systems, C6/ SSPE and C6/CDV, we observed a total loss of catecholamine-stimulated beta-adrenergic receptor-dependent methylation, whereas the beta-receptor-independent methylation of phospholipids was unchanged.

Adenylyl Cyclases↗
PubMed1982

Tolerance of the central nervous system to photon irradiation: endocrine complications.

Dose-response isoeffect equations have been determined for hypothalamic pituitary insufficiency following cranial irradiation. Of particular importance is the occurrence of complications at doses substantially less than those commonly used for the treatment of central nervous system tumors. Such complications may be severe and potentially life threatening. These complications occur when a small midline 'target' volume containing the pituitary gland, infundibulum and adjacent inferior hypothalamic structures is irradiated. Direct pituitary irradiation is unlikely to be a factor, at least in some cases. The possible role of incidental hypothalamic irradiation in the control of acromegaly and pituitary dependent Cushing's syndrome is discussed.

Brain↗
PubMed1981

Interferon induces an antiviral state in ganglioside-deficient transformed mouse fibroblasts.

The antiviral activity of mouse fibroblast interferon against vesicular stomatitis virus was investigated in L-929 mouse fibroblasts and the ganglioside-deficient L-929 mutant cells (ATCC clone NCTC 2071). Although it has been widely reported that gangliosides serve as primary receptors for interferon at the cellular membrane, only a small difference in interferon sensitivity was observed between the wild-type L-929 and the ganglioside-deficient NCTC 2071 cells. It was not possible, however, to overcome this difference by administration of exogenous gangliosides.

Animals↗
PubMed1981

Tolerance of the mature human central nervous system to photon irradiation.

Tolerance of mature human brain to photon irradiation is described. Isoeffect curves have been derived for tolerance of large and small volumes of brain, by examination of doses determined empirically and in clinical use. These have been compared with isoeffect curves of thoracic myelitis, optic nerve and chiasm damage, and brain necrosis. The results show that the best-fitting Ellis-type equations, when five fractions per week are used, have low exponents for overall treatment time and high exponents for the number of increments (N), and are similar to published data on rat myelitis. Of the equations used to test the relationship between total dose and number of increments, the power curve was the best fit. Mean values of exponents for N derived for brain and spinal cord tolerance were 0.4 or more. These were similar to values obtained for optic nerve and chiasm damage, though the data are more limited for this complication. Brain necrosis is observed at slightly higher doses probably because of a difference in the end-point observed rather than because of any fundamental difference in tissue response. Evidence is presented to suggest that some repopulation may occur in widely spaced schedules. The use of the Ellis equation derived from connective-tissue data is inappropriate for central nervous system tissue, and its use may lead to a substantial risk of overdosage. A plea is made for adequate documentation of treatment details when human data are reported. The importance of dose per fraction is emphasized.

Adult↗
PubMed1980

Persistent paramyxovirus infections and behaviour of beta-adrenergic receptors in C-6 rat glioma cells.

This paper describes the influence of persistent infections of C-6 rat glioma cells by paramyxoviruses [virus of subacute sclerosing panencephalitis (SSPE) and canine distemper (CDV)] on the cellular beta-adrenergic membrane receptors. The number and binding properties of the beta-adrenergic receptors of the paramyxovirus-infected cells were measured by 3H-dihydroalprenolol binding studies and compared with those of the uninfected C-6 cells. In the case of SSPE virus neither changes in number nor binding properties of beta-adrenergic receptors could be observed, whereas in the case of CDV persistence the number of beta-adrenergic receptors was reduced to about 50%, without an apparent influence on the binding constant for the ligand to the receptors.

Animals↗
PubMed1980

A hormone-independent rise of adenosine 3',5'-monophosphate desensitizes coupling of beta-adrenergic receptors to adenylate cyclase in rat glioma C6-cells.

An elevation of the intracellular cAMP concentration in C6 cells by cholera toxin or the cyclic nucleotide phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine causes a densitization of the beta-adrenergic-receptor-dependent synthesis of adenosine 3',5'-monophosphate. The specific binding of [3H]dihydroalprenolol to the beta-adrenergic receptors and the activation of the adenylate cyclase in vitro by fluoride anions and guanyl imidotriphosphate remain unchanged. It is likely that the desensitization is caused by an inhibition of beta-receptor coupling to the GTP-binding coupling protein in the adenylate cyclase complex. Furthermore, these experiments provide evidence that the loss of beta-receptor binding observed after incubation of cells with catecholamines is not a necessary consequence of the densensitization of receptor coupling dependent on adenosine 3',5'-monophosphate.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Impairment of hormone dependent signal transfer by chronic SSPE virus infection.

In a CNS-derived cell line, the cellular response to hormonal stimulation, represented by the rise of intracellular cAMP levels, is impaired under the influence of a persisting neurotropic virus infection. This dysfunction is caused by the decrease in adenylate cyclase activity, most probably due to the virus-induced loss of active catalytic units.

Adenylyl Cyclases↗
PubMed1979

Rabies virus infection selectively impairs membrane receptor functions in neuronal model cells.

A persistent infection with rabies virus (HEP-Flury) was established in the CNS-derived hybrid cell line 108CC15 which possesses specific membrane receptors for prostaglandins, catecholamines and acetylcholine. We report a differential virus influence on the specific receptor response to PGE, isoproterenol and acetycholine as indicated by typical changes of the intracellular cyclic AMP levels. As the adenylate cyclase activity was unchanged in infected cells in vitro, a selective virus influence on specific receptors themselves or their coupling to the cAMP synthesizing system must be considered.

Animals↗
PubMed1978

Interferon enhances the fragility of lysosomes in L-929 mouse fibroblasts.

Infection of interferon-treated L-929 mouse fibroblasts with vaccinia WR virus is followed by severe cytolysis within 3 to 4 h. It is shown that this cytolysis cannot be caused by enzymes released from lysosomes into the cytosol. However, there is evidence that homologous interferon has a noxious effect on lysosomes. This phenomenon appears to be another aspect of the anticellular functions of interferon.

Animals↗