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DOI: 10.1055/s-2000-4452
Effekt von Ambroxol auf die Surfactantsekretion und -synthese von isolierten, alveolären Typ-II-Zellen
Publication History
Publication Date:
31 December 2000 (online)
Zusammenfassung:
Ein Teil der Wirkung von Ambroxol wird auf eine Stimulation des Surfactantsystems zurückgeführt. Die Untersuchungen, die dem zugrunde liegen, geben eher indirekte Hinweise auf Surfactantsynthese und -sekretion. Ein direkter Nachweis der Stimulation von alveolären Typ II Zellen im Hinblick auf Synthese und Sekretion fehlt.
In dieser Untersuchung wurde eine direkter Effekt von Ambroxol auf die Surfactantsynthese und -sekretion untersucht. Dazu wurde die Freisetzung von markiertem Phosphatidylcholin unter dem Einfluss von Ambroxol in ansteigender Dosierung (10- 8M bis 10- 4M) und mit zunehmender Expositionszeit gemessen. Es fand sich weder mit zunehmender Konzentration noch mit zunehmender Zeit ein signifikanter Effekt des Ambroxol auf die Surfactantsekretion. Als Marker der Surfactantsynthese wurde die Aufnahme von 3H-markiertem Cholin und der Einbau in 3H-Phosphatidylcholin (PC) untersucht. Hier wurden ebenfalls ansteigende Konzentrationen (10- 7M bis 10- 5M) untersucht, und der zelluläre Gehalt an PC über 1, 2, 4, 8, 24 h verfolgt. Zu keinem Zeitpunkt fand sich eine signifikante Stimulation dieses Parameters durch Ambroxol in den getesteten Konzentrationen. Höhere Konzentrationen als die hier getesteten führten zu vermehrter LDH Freisetzung aus den isolierten AT-II-Zellen. Ambroxol, das auch antioxidative und antiinflammatorische Wirkungen besitzt, scheint also keine direkte Wirkung auf isolierte AT-II-Zellen (der Ratte) zu besitzen, wie dies zum Beispiel für die β2-Mimetika zutrifft. Eine spezifische, pharmakologische Möglichkeit der Stimulation des Surfactantsystems gilt es weiterhin zu entwickeln.
Effect of ambroxol on surfactant synthesis and secretion in isolated type II alveolar cells:
The effect of ambroxol is attributed in part to an effect on surfactant synthesis and secretion. Evidence supporting this hypothesis is largely indirect; a direct effect of ambroxol on surfactant synthesis and secretion remains to be demonstrated. In this study a direct effect of ambroxol was evaluated using isolated alveolar type II cells. Secretion of labelled phosphatidylcholine was measured following the addition of increasing concentrations (10- 8M to 10- 4M) of ambroxol to the culture medium for increasing time intervals. There was no significant increase in surfactant secretion with increased ambroxol concentration or prolonged exposure time. Uptake of 3H-choline and synthesis into 3H-phsophatidylcholine was analyzed as an indicator of surfactant synthesis. Again, increasing concentrations of ambroxol (10- 7M to 10- 5M) were followed for 1, 2, 4, 8 and 24 h. There was no significant effect on synthesis at any time point. Concentrations higher than those mentioned here resulted in LDH release from cultured cells. Ambroxol which also has anti-oxidative and anti-inflammatory effects does not exhibit direct stimulatory effects on surfactant synthesis and secretion in isolated (rat) alveolar type II cells as has been demonstrated e. g. for β2-adrenergic stimulation. A specific pharmacologic way to stimulate the surfactant system remains to be developed.
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Prof. Dr H Wirtz
Medizinische Klinik I und Poliklinik Universität Leipzig
Johannisallee 32 04103 Leipzig
Email: E-mail: wirtzh@medizin.uni-leipzig.de