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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 95-104 
    ISSN: 1432-1912
    Keywords: Temperature ; β-Receptors ; Guinea-Pig Atrium ; Affinity ; Adrenergic Drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using electrically stimulated guinea-pig atria the influence of temperature on the contractility and on the efficacy of some β-sympathomimetic and-lytic drugs, was studied. The following results were obtained. 1. Raising the temperature of the bath fluid from 25–42°C decreased significantly the developed amplitude of contraction under control conditions, whereas dT/dt max values were not altered. The maximal developed tension induced by the sympathomimetic drugs decreased at 42°C. The corresponding dT/dt max values, on the other hand, were increased by elevation of the temperature. 2. The dose-response curves of the sympathomimetic drugs isoprenaline (IPN), Th 1165a and orciprenaline (OPN) were shifted to the right when the temperature was increased from 25–42°C. The affinity of IPN at 33°C was found about 30- and 100-times higher than that of Th 1165a and OPN, respectively. 3. The β-adrenolytic drug pindolol (LB 46), as well as the cardioselective β-blocker, practolol, antagonized the β-sympathomimetic effects evoked by IPN and Th 1165a in a competitive manner. As indicated by the pA2 values, pindolol had a 100-times higher affinity than practolol. The present results lead to the conclusion that, on the guinea-pig atrium, the agonist β-receptor reaction depends on the metabolic rate of this organ.
    Type of Medium: Electronic Resource
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  • 2
    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.
    Type of Medium: Electronic Resource
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  • 3
    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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