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H Reuter

Publications and source records attributed to H Reuter.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of protein kinases in rat pheochromocytoma (PC12) cells promotes morphological differentiation and down-regulates ion channel expression.

We have studied morphological differentiation and ion channel expression in PC12 cells under different culture conditions. Differentiation mediated by nerve growth factor (NGF) was compared with that induced by depletion and inhibition of protein kinases (phorbol ester beta-PMA plus staurosporine). Morphological differentiation was similar under both conditions. However, ion channel densities, studied by means of the patch-clamp technique, were enhanced by NGF and reduced by beta-PMA+staurosporine. Similar changes were also observed for omega-conotoxin-sensitive Ca2+ channels by measuring radioligand binding. The decrease in Ca2+ channel density, after treatment of the cells with beta-PMA+staurosporine, resulted in a reduced increase in the intracellular Ca2+ concentration during K+ depolarization. We conclude that morphological differentiation, but not ion channel expression, can occur during depression of protein kinase activities in PC12 cells.

Alkaloids↗
PubMed1992

Activation of different pathways for calcium elevation by bradykinin and ATP in rat pheochromocytoma (PC 12) cells.

We have studied the pathways by which extracellular bradykinin and adenosine 5'-triphosphate (ATP) elicit changes in intracellular free calcium ([Ca2+]i) in nerve-growth-factor(NGF)- treated rat pheochromocytoma (PC 12) cells. Both substances caused a significant rise in [Ca2+]i as assessed by fura-2 based microfluorimetry. The bradykinin-induced response consisted of an initial Ca2+ mobilization from an internal pool followed by a sustained increase in [Ca2+]i, which was due to activation of a small inward current. The initial response always started at a localized site opposite to the cell nucleus. The inward current was partially carried by Ca2+ and began with a time lag of about 4 s after the start of the initial transient signal. Stepwise hyperpolarization of the plasma membrane, after activation of the inward current by bradykinin, caused a simultaneous increase in current amplitude and in [Ca2+]i, due to an increase in the driving force for Ca2+ influx. With ATP as an agonist the onset of inward current coincided with an increase in [Ca2+]i. Inward current and [Ca2+]i were enhanced during hyperpolarizing steps indicating a substantial Ca2+ influx through ATP-activated channels. No release of Ca2+ from internal stores, but a large Na+ inward current, was observed in Ca(2+)-free external solution after addition of ATP. While the bradykinin-induced responses were much more pronounced in cell bodies than in growth cones, the ATP effects were somewhat variable in cell bodies and more homogeneous in growth cones.

Adenosine Triphosphate↗
PubMed1991

Ionic channels: modulation by G proteins and by phosphorylation.

The gating of ion channels may be modulated by G proteins or by phosphorylation. Direct coupling between G proteins and ion channels has been shown in excised patches of membrane. Steps must now be taken to study the protein domains of G proteins and ion channels involved in the mutual interaction. The concept of channel modulation by protein kinases has recently been extended to include additional types of ion channel.

Animals↗
PubMed1991

The effects of aprotinin on hemostatic function during cardiac surgery.

The mechanism of action by which large doses of aprotinin decrease blood loss during cardiac surgery is not completely understood. In a prospective, controlled study, 30 patients undergoing cardiac surgery were given high-dose aprotinin in accordance with a commonly used regimen. Twenty untreated but otherwise comparable patients served as the control group. The effects of aprotinin therapy during cardiopulmonary bypass on coagulation parameters, the kallikrein-kinin system, fibrinolysis, platelet stimulation, and the release of elastase from neutrophils were studied. The fibrinolysis parameters were the only measurements that showed clear and significant differences between the two groups. Aprotinin almost completely inhibited the formation of fibrin and fibrinogen degradation products. It is assumed that inhibition of systemic fibrinolysis and suppression of local fibrinolysis contribute to the hemostatic action of aprotinin. The study did not demonstrate a significant protective effect of aprotinin on platelets. In addition, the dose of aprotinin administered did not affect the kallikrein-kinin system of elastase. Therefore, these data suggest that the previously demonstrated hemostatic effects of aprotinin derive primarily from its antifibrinolytic action.

Aged↗
PubMed1991

The polarized distribution of poly(A+)-mRNA-induced functional ion channels in the Xenopus oocyte plasma membrane is prevented by anticytoskeletal drugs.

Foreign mRNA was expressed in Xenopus laevis oocytes. Newly expressed ion currents localized in defined plasma membrane areas were measured using the two-electrode voltage clamp technique in combination with a specially designed chamber, that exposed only part of the surface on the oocytes to channel agonists or inhibitors. Newly expressed currents were found to be unequally distributed in the surface membrane of the oocyte. This asymmetry was most pronounced during the early phase of expression, when channels could almost exclusively be detected in the animal hemisphere of the oocyte. 4 d after injection of the mRNA, or later, channels could be found at a threefold higher density at the animal than at the vegetal pole area. The pattern of distribution was observed to be similar with various ion channels expressed from crude tissue mRNA and from cRNAs coding for rat GABAA receptor channel subunits. Electron microscopical analysis revealed very similar microvilli patterns at both oocyte pole areas. Thus, the asymmetric current distribution is not due to asymmetric surface structure. Upon incubation during the expression period in either colchicine or cytochalasin D, the current density was found to be equal in both pole areas. The inactive control substance beta-lumicolchicine had no effect on the asymmetry of distribution. Colchicine was without effect on the amplitude of the expressed whole cell current. Our measurements reveal a pathway for plasma membrane protein expression endogenous to the Xenopus oocyte, that may contribute to the formation and maintenance of polarity of this highly organized cell.

Animals↗
PubMed1991

Dependence of cytosolic calcium in differentiating rat pheochromocytoma cells on calcium channels and intracellular stores.

1. The rat clonal pheochromocytoma cell line (PC12) was used to study changes in the free intracellular Ca2+ concentration [( Ca2+]i) that are related to the distribution of L-type (dihydropyridine-sensitive) and N-type (omega-conotoxin-sensitive) calcium channels during nerve growth factor (NGF)-induced outgrowth of neurites. Changes in [Ca2+]i during K+ depolarization were recorded by means of Fura-2 single-cell microfluorimetry. 2. The basal [Ca2+]i of cells at rest was not altered by long-term treatment with NGF, neither in the cell bodies nor in the growth cones. K+ depolarization of the cells caused a rise in [Ca2+]i. 3. The dihydropyridine (DHP) nifedipine alone, or together with omega-conotoxin (omega-CgTX), were similarly effective in inhibiting the K(+)-induced increase in [Ca2+]i in untreated and NGF-treated cell bodies, arguing for a preferential distribution of L-type Ca2+ channels in this cell area. By contrast, after 6-7 days exposure to NGF the K(+)-induced initial transient rise of [Ca2+]i in growth cones was very sensitive to omega-CgTX, whereas nifedipine affected only the sustained rise. 4. PC12 cells also contain caffeine- and inositol trisphosphate (IP3)-sensitive intracellular Ca2+ stores. Addition of 30 mM-caffeine caused a fast transient rise in [Ca2+]i. The extent of filling of the caffeine-sensitive pool affected basal [Ca2+]i. These Ca2+ storage sites were empty under normal culture conditions. However, a single K+ depolarization caused filling of the stores, followed by spontaneous depletion (50% in about 5 min) after wash-out of high [K+]o. When the caffeine-sensitive stores were empty, the rise in [Ca2+]i was attenuated during submaximal depolarization. Caffeine-sensitive Ca2+ stores were also present in some growth cones, though with much smaller capacities than in cell bodies. 5. Mobilization of Ca2+ from the IP3-sensitive store, by bradykinin exposure, was found to be independent of the caffeine-sensitive pool. There was no apparent 'cross-talk' between both Ca2+ pools. 6. We conclude that changes in [Ca2+]i in cell bodies depend on both membrane Ca2+ channels and intracellular Ca2+ stores. During NGF-induced differentiation there is a predominance of N-type Ca2+ channels in growth cones, while Ca2+ stores are of minor importance in these structures.

Animals↗
PubMed1991

Regulation of bradykinin- and ATP-activated Ca(2+)-permeable channels in rat pheochromocytoma (PC12) cells.

Membrane currents activated by bradykinin (500 nM) and by extracellular ATP (50 microM) were studied in voltage-clamped, NGF-treated rat pheochromocytoma (PC12) cells. Under quasiphysiological ionic conditions, both substances caused an outward current due to opening of Ca(2+)-activated K+ channels. Bradykinin caused an additional inward current that could be studied after blockade by internal Cs+ of the initial transient outward current. The inward current became larger when the extracellular Ca2+ concentration was increased. Neither inositol-1,4,5-trisphosphate, dioctanoylglycerol, phorbol 12-myristat 13-acetate, forskolin, GTP, GTP-gamma-S, or pretreatment with pertussis toxin affected this current component. Increasing the internal Ca buffer concentration [EGTA or bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid] from 1 to 10 mM had no effect on the inward current as long as the free [Ca2+]i was kept constant. However, it was modulated by the resting free [Ca2+]i. Elevation of [Ca2+]i from nominally 0 to 60 or to 180 nM increased the bradykinin-induced average peak current density from 0.14 to 1.04 or to 2.29 pA/pF, respectively. This regulation may depend on a calmodulin-dependent pathway, since CGS 9343B, a calmodulin inhibitor, blocked the effect of elevated [Ca2+]i. With ATP as an agonist, outward current was preceded by a large inward current that was partially blocked by extracellular Ca2+ in the millimolar range. Extracellular Ca2+ was also found to reduce the single-channel conductance estimated from outside-out patches treated with ATP.

Adenosine Triphosphate↗
PubMed1990

Differential expression by nerve growth factor of two types of Ca2+ channels in rat phaeochromocytoma cell lines.

1. Two clones of rat phaeochromocytoma PC12 cells have been used to study the expression of Ca2+ channels and their possible involvement in neuronal differentiation. One clone differentiated morphologically when exposed to nerve growth factor (NGF) for 4 days (PC12 cells), while the other clone was insensitive to NGF, but differentiated morphologically in the presence of ouabain (0.1 mM) for 7 days (PC12-mutant cells). 2. Whole-cell Ba2+ currents through Ca2+ channels were measured in PC12 cells at a test potential (Et) of +10 mV, from two holding potentials (Eh) of -90 and -30 mV (I-90 and I-30). NGF-induced differentiation increased I-90 by 248% and I-30 by 133%. The cells that differentiate in the presence of ouabain had only small, if any, Ba2+ currents that did not appear to change during morphological differentiation or after the addition of NGF. 3. Barium currents in PC12 cells could be separated into two components by selective antagonists. The component of I-90 that could be inhibited by omega-conotoxin GVIA (omega-CgTX) in NGF-differentiated cells was 458 +/- 84 pA (mean +/- S.E.M.), compared with 79 +/- 44 pA in native cells. I-30 was reduced by 50 +/- 17 pA in NGF-treated cells and was virtually insensitive to the toxin in native cells. By contrast, the dihydropyridine (DHP) isradipine reduced I-30 in NGF-treated cells by 30 +/- 8 pA and in native cells by 20 +/- 3 pA. 4. Radioligand binding studies with 125I-omega-CgTX in PC12 cell membrane fragments and in PC12 cells showed a 2- to 3-fold increase in maximal binding capacity after NGF exposure, while mutant cells showed no such change in binding capacity after treatment with NGF or ouabain. Staurosporine inhibited the effect of NGF on 125I-omega-CgTX binding. [3H](+)-isradipine binding capacity was increased 1.8-fold by NGF in depolarized PC12 cells while no change was observed in mutant cells after NGF or ouabain. There was no interaction between omega-CgTX and DHP binding sites. 5. Both the electrophysiological and the binding data indicate a preferential expression of omega-CgTX-sensitive Ca2+ channels (N type) over isradipine-sensitive channels (L type) in PC12 cells treated with NGF. By contrast, ouabain-induced differentiation of a mutant PC12 cell line, that lacks functional NFG receptors, was not associated with the expression of Ca2+ channels.

Adrenal Gland Neoplasms↗
PubMed1990

[Noncardiac risk factors in heart surgery--the blood coagulation system].

Diagnostics and therapy in coagulation disorders are presented. A special emphasis is given to alterations of blood coagulation in cardiac surgery. No major rule can be defined for this particular field. All disturbances of blood coagulation may become clinically overt in highly variable combinations, thus representing no or high risk to patients conditions. This implies that the actual risk has to be estimated individually for every patient and that the risk of the cardiac disorder has to be considered in view of the risk of the operation plus potential disturbances in coagulation. The latter in order to be assessed appropriately, clearly requires a laboratory specialised in diagnostics of coagulation, as well as a highly experienced coagulation physiologist for decision making. Following this policy, we have not been forced to disagree about extracorporeal circulation for cardiac surgery in most instances. Problems have been confined to patients suffering from various hepatic disorders or from impaired platelet functions.

Blood Coagulation Disorders↗
PubMed1979

The utilisation of a new strength citrate anticoagulant during centrifugal plateletpheresis. III. Assessment of in vitro platelet metabolism.

Employing the Haemonetics Blood Processor (IFC), a relatively pure platelet concentrate can be prepared by collecting only the first portion of the PRP leaving the centrifuge bowl (Fraction I). A subsequent fraction containing RBC and WBC contaminants (Fraction II) can be purified by means of a second centrifugation, using a conventional blood bank centrifuge (Fraction II), if transfusion of these contaminants would be detrimental to the recipient. Utilising the new 1.4% Na3-citrate anticoagulant, platelet metabolic parameters (ATP, ADP, AMP, lactate and pyruvate) as well as O2-uptake, were determined in Fraction I and II prepared from 10 normal healthy subjects. In contrast to previous studies reporting marked dysfunction in platelets contained in Fraction II when standard ACD-A was used during IFC, we observed no significant difference (Student's t test) in the present study between Fractions I and II, in regard to platelet metabolism, when using the new anticoagulant. It is further concluded that the second centrifugal manipulation does not exert a detrimental effect on platelet metabolism.

Anticoagulants↗
PubMed1979

[Studies in medical meteorology at the "Zentralanstalt für Meteorologie und Geodynamik" at Vienna (author's transl)].

Weather situations connected with small pressure gradients show a statistically significant correlation with the liability to heart-attacks. Changes from cyclonic to anticyclonic situations with descending air-motion lead to a rise of the number of heart-attacks in summer. In winter the change from anticyclonic to cyclonic pressure distributions seems to be critical.

Air Movements↗
PubMed1978

Platelet metabolism.

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Adenosine Diphosphate↗