Summary
The effects of l-Dopa and the dopamine receptor stimulant ET-495 on cisternal cAMP levels were studied in rats. l-Dopa (100–200 mg/kg) increased cisternal cAMP levels by 60 to 80% of controls. When peripheral Dopa-decarboxylase was inhibited, smaller doses of l-Dopa were effective. Fla-63, an inhibitor of dopamine-β-hydroxylase lowered the increase induced by l-Dopa which was completely suppressed by propranolol, not by phentolamine, suggesting that the cAMP increase is mediated through a central β-adrenoceptor stimulation. ET-495 failed to influence cAMP levels which argues against a dopamine-sensitive adenylate cyclase involved in the l-Dopa effect. Moreover, large increases of cisternal cAMP were observed after treatment with theophylline, not papaverine which suggests different effects of these “phosphodiesterase inhibitors” on the cyclic AMP systems in the central nervous system or on transport mechanisms.
Zusammenfassung
Die Wirkung von l-Dopa und dem Dopaminagonisten ET-495 auf die cisternale cAMP-Konzentration wurde bei Ratten untersucht. l-Dopa (100–200 mg/kg) erhöhte die cAMP-Spiegel um 60–80%. Den gleichen Effekt hatten geringere l-Dopa-Dosen nach Hemmung der extracerebralen Dopa-Dekarboxylase. Vorbehandlung mit dem Dopaminβ-Hydroxylase-Hemmer Fla-63 verminderte die Wirkung von l-Dopa, welche durch Propranolol völlig unterdrückt wurde. ET-495 beeinflußte die cisternale cAMP-Konzentration nicht. Es wird geschlossen, daß der cAMP-Anstieg nach l-Dopa-Anwendung über einen zentralen noradrenergen Mechanismus mit Stimulierung eines β-adrenergen Adenylatcyklase-Receptors zustande kommt. Es wird ferner gezeigt, daß Theophyllin, nicht aber Papaverin, die cAMP-Konzentration im Liquor stark erhöht, was unterschiedliche Wirkungen der beiden „Phosphodiesterasehemmer“ auf den Stoffwechsel oder Transport von cAMP nahelegt.
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Supported by the Deutsche Forschungsgemeinschaft (SFB 70). Work presented in this paper is part of a thesis to be submitted to the Medical Faculty of the University of Freiburg (M. K.).
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Kießling, M., Lindl, T. & Cramer, H. Cyclic adenosinemonophosphate in cerebrospinal fluid. Arch. Psychiat. Nervenkr. 220, 325–333 (1975). https://doi.org/10.1007/BF00342062
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DOI: https://doi.org/10.1007/BF00342062