Summary
1. In isolated fat pads of rats the dibutyryl derivative of cyclic 3′,5′-AMP (DBA) proved to be 100 times more active in promoting lipolysis than 3′,5′-AMP itself; hormones (ACTH, Norepinephrine) were about 10.000 times more active than DBA. Inhibition of phosphodiesterase by theophylline potentiated the lipolytic effect of DBA as well as that of the hormones.
2. In isolated adrenals of rats the stimulatory effect of DBA on corticosterone synthesis was approximately 100 times greater than that of 3′,5′-AMP, but 500 times less than that of ACTH. In contrast to lipolysis, the stimulatory effect of the nucleotides and ACTH on the adrenals was not enhanced by theophylline, but was rather inhibited by high doses of the xanthine derivative.
3. In unanesthetized rats the hyperglycemic action of intraperitoneally injected DBA was much greater than that of 3′,5′-AMP: In order to elevate blood glucose by 40 mg/100 ml, 1 μmole/kg of DBA but 30 μmoles/kg of 3′,5′-AMP were necessary. Pretreatment of the animals with theophylline did not potentiate this action of the nucleotides.—The level of plasma free fatty acids and glycerol was not elevated by DBA but was rather depressed. Only very high doses of DBA increased the level of plasma corticosterone.
The results are discussed in connection with the second messenger concept of Sutherland and coworkers.
Zusammenfassung
1. Am isolierten Fettgewebe von Ratten hatte das Dibutyrylderivat des cyclischen Adenosin-3′,5′-Monophosphat (DBA) eine etwa 100 mal stärkere lipolytische Wirkung als das nicht substituierte cyclische Adenosin-3′,5′-Monophosphat (3′,5′-AMP). Hormone (ACTH, Noradrenalin) waren an diesem Testobjekt 10000 mal wirksamer als DBA. Durch Hemmung der Phosphodiesterase mit Theophyllin ließ sich auch die Wirkung des DBA verstärken.
2. An isolierten Nebennieren von Ratten stimulierte DBA die Corticosteronsynthese etwa 100 mal stärker als 3′,5′-AMP; ACTH war aber 500 mal wirksamer als DBA. Durch Theophyllin ließ sich die Wirkung von ACTH, DBA bzw. 3′,5′-AMP nicht verstärken. Hohe Konzentrationen des Xanthinderivates hemmten die Corticosteronsynthese.
3. An Ratten war die hyperglykämische Wirkung des DBA wesentlich stärker als diejenige des 3′,5′-AMP: Für eine Erhöhung des Blutzuckerspiegels um 40 mg/100 ml benötigten wir von DBA weniger als 1 μmol/kg, von 3′,5′-AMP aber 30 μmol/kg. Diese Wirkung der Nucleotide ließ sich durch Theophyllin nicht verstärken. Der Fettsäuren- und Glyceringehalt des Plasmas wurde durch Injektion von DBA bzw. 3′,5′-AMP nicht erhöht, sondern erniedrigt. — Die Ergebnisse wurden im Zusammenhang mit dem “Second Messenger Concept” von Sutherland u. Mitarb. diskutiert.
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Herrn Prof. Dr. L. Lendle zum 70. Geburtstag gewidmet.
Über einen Teil der Ergebnisse wurde auf der 8. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft (Stock u. Westermann, 1967; Bieck u. Westermann, 1967) sowie in einer kurzen Mitteilung (Bleck et al., 1968) berichtet.
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Bieck, P., Stock, K. & Westermann, E. Wirkung von cyclischem Adenosin-3′,5′-Monophosphat (3′,5′-AMP) und seinem Dibutyrylderivat (DBA) auf Lipolyse, Glykogenolyse und Corticosteronsynthese. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 263, 387–405 (1969). https://doi.org/10.1007/BF00538773
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DOI: https://doi.org/10.1007/BF00538773