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  • Allergic asthma  (3)
  • Isolated Organs  (3)
  • Down-regulation  (2)
  • 1
    ISSN: 1432-1440
    Keywords: Β-Adrenoceptors ; Mononuclear leukocytes ; Right atrium ; Down-regulation ; Catecholamines ; Congenital heart disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sympathetic regulation of myocardial performance has been shown to be altered in congestive heart failure. Right atrial tissue of children with severe acyanotic and cyanotic congenital heart disease (CHD) showed a significantly lowerΒ-receptor density than that of children with less severe defects. Since mononuclear leukocytes (MNL) contain a homogeneous population ofΒ 2-adrenoceptors which have similar properties to those of cardiacΒ 2-adrenoceptors, they are frequently used for studying theΒ-adrenergic system. In a group of 37 children with CHD of different types and severity who underwent cardiac surgery, we compared the MNLΒ-adrenoceptor density to the type and severity of CHD and looked for a possible relationship to plasma catecholamine levels and to the right atrialΒ-adrenoceptor density. Membranes of MNL and myocardial cells were radiolabeled with (−)3-[125I]Iodocyanopindolol ([125I]ICYP). A significantly higherΒ-adrenoceptor density on MNL was found in patients with moderate acyanotic CHD (group I) than in those with severe acyanotic (group II) and cyanotic CHD (group III). Patients of group I showed approximatively 50% higher myocardialΒ-receptor density than those of groups II and III. ICI 118.551-[125I]ICYP competition studies revealed that in groups II and III significantly lower proportions and densities ofΒ 1-receptors were found compared to group I. Noradrenaline (NA) plasma levels in group II and group III were significantly higher than those in group I. The adrenaline plasma levels were found to be very high in all children with CHD. A significant negative correlation between NA levels and myocardial total andΒ 1-adrenoceptor density, but no correlation between plasma catecholamines and MNLΒ-adrenoceptor density, was calculated. We conclude that modulation of MNLΒ-adrenoceptors is not simply controlled by circulating catecholamine levels. CardiacΒ 2-adrenoceptor density remained unaltered, but theΒ 1-density was significantly lowered.Β 2-adrenoceptors on MNL showed a slight but significant decrease. However, cardiacΒ 2-adrenoceptor density cannot be predicted by measuring theΒ-adrenoceptor density on MNL.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 105-113 
    ISSN: 1432-1912
    Keywords: Sympathomimetic Affinity ; β-Receptors ; Temperature ; Metabolic State ; Isolated Organs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments on isolated organs-rabbit ileum, guinea-pig trachea and atrium — with different “β-receptor subtypes” were carried out in order to determine whether changes of the metabolic state or of the extracellular pH were able to alter the responsiveness of these receptors to sympathomimetic amines. 1. Guinea-Pig Atrium. Lowering of the pH of the bath fluid from 7.48 to 6.79 resulted in a significant decrease of the affinity of isoprenaline (IPN) calculated as the pD2-value. Metabolic inhibition induced by iodoacetic acid (IAA) (5×10−5 M) increased the affinity of Th 1165a. 2. Rabbit Ileum. The affinity of IPN was not changed by lowering the pH, even to values of 6.11. At this pH the spontaneous motility was already markedly impaired. IAA (2.4×10−5 M) caused a moderate increase in the affinity of IPN whereas those of Th 1165a and orciprenaline (OPN) were elevated 10-fold. 3. Guinea-Pig Trachea. Lowering of the pH caused a decrease of the pD2-values of IPN and in particular of Th 1165a. The metabolic inhibitor IAA had no influence upon the pD2 value of IPN. 4. The present results favour the existence of only one type of β-receptor which changes its sensitivity depending on the metabolic state. It seems therefore very likely that the affinity of sympathomimetic drugs depends not only on the structure of the β-receptor but also on the metabolic state of the tissue.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Exercise induced asthma ; Allergic asthma ; Histamine ; Catecholamines ; Theophylline ; Plasma levels ; Anstrengungsasthma ; allergisch-bedingtes Asthma ; Histamin ; Katecholamine ; Theophyllin ; Plasmaspiegel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Um zu untersuchen, ob endogene Transmitter bei der Auslösung und Unterhaltung verschiedener Formen des Asthma bronchiale eine Rolle spielen, haben wir bei Kindern vor und nach einer Laufbelastung sowie vor und nach einer inhalativen Provokation mit wäßrigen Allergenextrakten das Serumhistamin, Serumnoradrenalin und den bronchialen Strömungswiderstand (Rt) bestimmt. Die Untersuchung zeigt, daß das Belastungsasthma mit einem starken Anstieg des Plasmanoradrenalins, nicht jedoch des Plasmahistamins einhergeht. Dieser Anstieg war wesentlich ausgeprägter als der bei einem asthmatischen Vergleichskollektiv ohne Anstrengungsasthma. Im Gegensatz dazu zeigten die Kinder, die nach einer Allergenprovokation einen Asthmaanfall entwickelten, einen signifikanten Histamin-, jedoch keinen Noradrenalinanstieg. Zwischen Histamin-Serumspiegel und Stärke der Bronchokonstriktion bestand eine gute Korrelation (r=0.98). Nach oraler Applikation übte Theophyllin einen Schutz sowohl gegenüber dem Anstrengungsasthma, als auch gegenüber dem allergisch bedingten Asthma aus. Da Theophyllin beim allergisch ausgelösten Asthma nicht nur zu einem Abfall von Rt führte, sondern auch den Histaminanstieg verminderte, kann vermutet werden, daß ein Teil der Wirkung dieser Substanz beim allergischen Asthma auf einer Hemmung der Histaminfreisetzung beruht. Die Noradrenalinfreisetzung beim Anstrengungsasthma beeinflußte es nicht. Für seine protektive Wirkung bei dieser Asthmaform müssen daher andere Wirkungsmechanismen angenommen werden. Ob diese ausschließlich auf einer Relaxation beruhen, muß ungeklärt bleiben. Als Schlußfolgerung dieser Untersuchung wird deutlich, daß das Anstrengungsasthma und das allergische Asthma 2 verschiedene Typen eines Syndroms sind. Arzneimittel, die gegenüber beiden Typen wirksam sind, können dies über verschiedene Wirkungsmechanismen tun.
    Notes: Summary To investigate whether endogenous transmitters play a role in different forms of bronchial asthma we determined histamine and noradrenaline plasma levels as well as airway resistance (Rt) before and after exercise and allergen challenge in children. The study demonstrates that in exercise induced asthma (EIA) broncho-constriction was paralleled by increases of noradrenaline, but not of histamine plasma levels. This increase of noradrenaline was much more pronounced than that observed in the asthmatic control group not suffering from EIA. In contrast to what has been observed in EIA, bronchoconstriction in response to allergen challenge was closely associated with increases of histamine, but not of noradrenaline plasma levels. Between histamine concentrations and severity of illness a good correlation was found (r=0.98). Tests carried out after oral administration of theophylline showed a protection against EIAand allergic induced asthma. Since theophylline in allergic asthma concomitantly reduced the increase in Rt and plasma histamine it is suggested that at least part of the beneficial effects of theophylline in allergic asthma may result from inhibition of histamine release. In those children suffering from EIA theophylline did not affect noradrenaline release. Thus, consideration must be given to effects of theophylline against EIA which are based on other mechanisms. Whether these effects are solely attributable to relaxation of bronchial smooth muscle or not remains to be clarified. In conclusion this study clearly has identified exercise and allergic induced asthma as different types of the syndrome that we call asthma. Drugs which prevent against both types may do this by different modes of action.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1076
    Keywords: β-adrenoceptors ; Down-regulation ; Catecholamines ; Congenital heart disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-six infants and children with congenital heart disease (CHD) undergoing cardiac surgery were investigated for alterations in myocardial β-adrenoceptor density. The patients were divided into three groups according to type and severity of CHD: group I consisted of 6 patients with acyanotic shunt lesions of moderate severity; group II comprised 13 children with severe acyanotic shunt and valve lesions and group III included 7 children with cyanotic CHD. The myocardial β-adrenoceptor density was determined using (−)3-[125I] Iodocyanopindolol ([125I]ICYP) and was reduced by approximately 50% in severe acyanotic CHD (33.6 fmol/mg protein) and cyanotic CHD (35.3 fmol/mg protein) in comparison with the group with less severe acyanotic shunt defects (64.4 fmol/mg protein). The affinity dissociation constant (K d, ICYP) did not differ statistically between the groups. The proportion of β1- and β1-subpopulation was evaluated by ICI 118,551-[125I]ICYP competition studies. In group II (61.5%) and group III (69.1%) significant lower portions of β1-adrenoceptors were found compared with group I (78.2%). This shift of subpopulations was due to a decreased β1-receptor density while β2-receptor density was unchanged in all groups. While the plasma noradrenaline levels of group I were similar to those of a control group of 13 healthy children, respective values of group II and III were significantly elevated. A significant negative correlation was found between plasma noradrenaline levels and myocardial β-adrenoceptor density. It is concluded that exposure of these receptors to increased circulating catecholamines, due to an enhanced sympathetic tone, leads to a reduction of their density. Noradrenaline, a preferential agonist of β1-adrenoceptors, is most probably responsible for the shift of the β-adrenoceptor subpopulations from the β1- to β2-subtype, depending on severity and type of cardiac disease.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 134 (1980), S. 45-50 
    ISSN: 1432-1076
    Keywords: Exercise induced asthma (EIA) ; Catecholamines ; Cyclic AMP ; a-Adrenergic blockade ; Allergic asthma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to provoke exercise induced asthma (EIA) a test which involved running for 7 min was performed with 21 asthmatic children. Eleven children not only developed a highly significant increase in airway resistance (Rt), but showed also a 4-fold increase in plasma noradrenaline (NA) levels. In 10 children who did not develop EIA only a 1.5-fold increase of NA could be observed. Following exercise cyclic AMP showed an identical increase in both groups studied, whereas adrenaline levels remained uninfluenced. Tests carried out after administration of phentolamine by inhalation showed a significant inhibition of post-exercise bronchoconstriction. It is concluded that EIA originates from a-receptor stimulation which is mediated by excessive noradrenaline release. However, since disodium cromoglycate—which does not act via adrenergic mechanisms—also protected against EIA, other factors should be involved. In 5 children with allergic asthma, asthmatic attacks were accompanied by a significant decrease in cAMP, whereas noradrenaline levels remained uninfluenced. Thus, evidence appears that both types of asthma result from different autonomic dysfunctions.
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  • 6
    ISSN: 1432-1076
    Keywords: Allergic asthma ; Children ; Phospholipids ; Fatty acids ; Glucocorticoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fatty acid (FA) composition of plasma phospholipids and phospholipids extracted from peripheral mononuclear white blood cells (MNC) was investigated in 11 allergic asthmatic children (age 8.9±4.6 years), in 10 age-matched non-allergic healthy controls and in 14 allergic and non-allergic children with an acute attack of asthma, who had received prednisolone medication for 2–4 days. In allergic asthmatics eicosapentaenoic acid (20∶5n−3) was significantly elevated in both plasma and MNC. The relative amount of 20∶5n−3 in MNC as well as in plasma correlated positively with increasing levels of total serum IgE (P〈0.02). The pattern of the other FAs in plasma and of MNC phospholipids did not differ between allergic asthmatic and non-allergic control children. In children with an acute attack of asthma, who had been treated with glucocorticoids (2 mg prednisolone/kg body weight for 2–4 days), distinct changes of relative FA composition of phospholipids were restricted to plasma, where some very long chain FA (22∶4n−6, 22∶5n−6) were elevated. No significant changes in FA from MNC phospholipids could be observed after glucocorticoid treatment. These findings may indicate a possible role of 20∶5n−3, the precursor of “group 3” eicosanoids, in allergic asthmatic children.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 63-70 
    ISSN: 1432-1912
    Keywords: Isolated Organs ; Adrenergic α- and β-Receptors ; Temperature ; Metabolic Inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Under the conditions of altered temperature or metabolic inhibition experiments have been carried out on isolated organs with adrenergic α- and β-receptors, i.e., on rabbit ileum and guinea-pig vas deferens and atrium. Using phenylephrine as a selective α-adrenergic stimulant we were interested to determine whether or not an alteration of the metabolic conditions was capable of causing changes in the affinity of phenylephrine which were identical for the α- and β-receptors. 1. Rabbit Ileum. At 25°C the affinity of phenylephrine to the inhibitory adrenergic α-receptors was 100 times higher than to the β-receptors. Its affinity to the α-receptors was not influenced by raising the temperature or inhibiting the metabolic rate by iodoacetic acid (IAA), whereas that to the β-receptors was diminished to a great extent by raising the temperature. Preincubation at 42°C with the metabolic inhibitor IAA increased the affinity to β-receptors so that it was similar to that at 25°C. 2. Vas Deferens. The excitatory α-mimetic effect of phenylephrine was similarly unaltered by raising the temperature of the bath from 25° to 42°C. IAA did not affect responses to phenylephrine. 3. Guinea-Pig Atrium. An increase of the temperature from 25° to 42°C significantly decreased the affinity of phenylephrine to the β-receptors, whereas IAA at 42°C increased it almost to control values at 25°C. 4. The experiments show that the sensitivity of α-receptors is not altered by an increase of temperature irrespective of whether the α-receptors are mediating inhibitory or excitatory effects, whereas that of the β-receptors is depressed. These results favour the hypothesis that stimulation of α-receptors is independent of, while that of the β-receptors is strongly dependent on the metabolic rate.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 284 (1974), S. 245-261 
    ISSN: 1432-1912
    Keywords: Phenylephrine ; Isolated Organs ; Competitive Dualism in Action ; Local Anaesthesia ; Antiarrhythmic Activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The β-sympathomimetic effect of phenylephrine was investigated on the electrically driven atrium, as well as on the tracheal chain of the guinea pig. 1. Phenylephrine (PE) was found to be less effective than isoprenaline (IPN) with regard to its positive inotropic effect on the guinea-pig atrium and to its relaxing action on the tracheal chain. The intrinsic activity for PE amounted to 0.75 on the tracheal chain and to 0.45 on the atrium, when compared with IPN. 2. From these low intrinsic activities, PE was assumed to be a partial β-agonist, exerting a competitive dualism in action to IPN. This dualism could be confirmed by dose-response curves for PE in the presence of IPN and vice versa: PE behaved as a β-agonist as well as a β-antagonist. 3. The intrinsic activity of PE steadily decreased with prolongation of the incubation period. After 1 h PE had almost lost its intrinsic activity. Under these conditions the dose-response curves for IPN on the tracheal chain, as well as on atrium, were shifted to the right in a parallel manner, i.e. PE behaved as a competitive β-antagonist. 4. High concentrations of PE (10−3 M) protected the electrically driven guineapig atrium against arrhythmias induced by k-strophanthoside. The onset of both the first extrasystoles and of heart standstill, which occurred after infusion of k-strophanthoside, were delayed after preincubation with PE. 5. Phentolamine was without any influence on these antiarrhythmic properties of PE. Therefore, it could be excluded that the antiarrhythmic effect of phenylephrine is due to a stimulation of myocardial α-adrenoceptors. 6. The local anaesthetic activity of phenylephrine, as tested on the rabbit cornea, was 4 times higher than that of propranolol. 7. The effective concentrations for the β-adrenolytic, antiarrhythmic, and local anaesthetic activities of PE were clearly different. We concluded, therefore, that the different actions produced by phenylephrine were not associated with each other.
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