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Direct characterization ofΒ-adrenoceptors in membranes of immature red blood cells from rats

Direkte CharakterisierungΒ-adrenerger Rezeptoren in MembranprÄparationen unreifer Erythrozyten der Ratte

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Zusammenfassung

Mittels des radioaktiv markierten Antagonist-Liganden (3H) (−) Dihydroalprenolol (DHAP) wurden spezifische Bindungsstellen in Membran-PrÄparationen von Erythrozyten der Ratte identifiziert, die aus folgenden Gründen alsΒ-adrenerge Rezeptoren angesprochen werden können: Im Gegensatz zur unspezifischen Bindung von DHAP war die spezifische Bindung abhÄngig von der Inkubationszeit und der Temperatur. Sie folgte einer SÄttigungskinetik, war — in AbhÄngigkeit von der Temperatur — reversibel und wies eine hohe AffinitÄt auf (KD für DHAP = 6,51 nM). Die rezeptorspezifische Bindung von DHAP wurde durchΒ-Rezeptorenblocker (Pindolol > Alprenolol ≧ Propranolol > Practolol) oderΒ-Sympathomimetika (Isoprenalin > Adrenalin) kompetitiv gehemmt. Die (−) Enantiomeren von Pindolol und Isoprenalin hatten eine wesentlich höhere AffinitÄt als die antsprechenden (+) Enantiomeren. Die Dichte Β-adrenerger Rezeptoren (pmole/mg Eiwei\) nahm mit steigendem Retikulozytosegrad zu: Sie stieg auf das 4-bis 5fache an, wenn die Retikulozytenwerte durch Vorbehandlung der Tiere mit Azetylphenylhydrazin von 3 auf 80 % gesteigert wurden.

Summary

By means of the radioactive antagonist ligand (3H) (−) dihydroalprenolol (DHAP) specific binding sites were identified in membrane preparations from red blood cells from rats. These specific sites were characterized asΒ-adrenoceptors because of the following reasons: Specific binding of DHAP (in contrast to unspecific binding) was dependent on temparature and time of incubation. Furthermore, specific binding of DHAP showed saturability, temperature-dependent reversibility and high affinity (KD-value of DHAP = 6.51 nM). Specific binding of DHAP was competitively inhibited byΒ-adrenergic antagonists (pindolol > alprenolol ≧ propranolol > practolol) and agonists (isoprenaline > adrenaline). The (−) enantiomers of pindolol and isoprenaline showed pronounced higher affinities for the receptor sites than the respective (+) enantiomers. The receptor density in the membrane preparations (pmoles/mg protein) was strongly dependent on the degree of reticulocytosis: The Bmax-values increased more than 4 to 5 fold without alteration of the respective KD-values when reticulocyte counts were enhanced from 3 to 80 % treatment of the animals with increasing doses of acetyl phenylhydrazine.

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  1. Zentrum der Pharmakologie, Klinikum der Johann-Wolfgang-Goethe-UniversitÄt, Theodor-Stern-Kai 7, D-6000, Frankfurt am Main, Germany

    G. Kaiser, G. Wiemer, J. Dietz & D. Palm

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  1. G. Kaiser
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  2. G. Wiemer
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  3. J. Dietz
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  4. D. Palm
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Kaiser, G., Wiemer, G., Dietz, J. et al. Direct characterization ofΒ-adrenoceptors in membranes of immature red blood cells from rats. Blut 37, 295–306 (1978). https://doi.org/10.1007/BF01007864

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  • DOI: https://doi.org/10.1007/BF01007864

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